Review Article Mitochondria-Targeted Protective Compounds in …downloads.hindawi.com/journals/omcl/2015/408927.pdf · 2019-07-31 · Review Article Mitochondria-Targeted Protective

Review ArticleMitochondria-Targeted Protective Compounds inParkinsonrsquos and Alzheimerrsquos Diseases

Carlos Fernaacutendez-Moriano Elena Gonzaacutelez-Burgos and M Pilar Goacutemez-Serranillos

Department of Pharmacology Faculty of Pharmacy University Complutense of Madrid 28040 Madrid Spain

Correspondence should be addressed to M Pilar Gomez-Serranillos pserraucmes

Received 30 December 2014 Revised 25 March 2015 Accepted 27 March 2015

Academic Editor Giuseppe Cirillo

Copyright copy 2015 Carlos Fernandez-Moriano et al This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Mitochondria are cytoplasmic organelles that regulate both metabolic and apoptotic signaling pathways their most highlightedfunctions include cellular energy generation in the form of adenosine triphosphate (ATP) regulation of cellular calciumhomeostasis balance between ROS production and detoxification mediation of apoptosis cell death and synthesis andmetabolismof various keymolecules Consistent evidence suggests that mitochondrial failure is associated with early events in the pathogenesisof ageing-related neurodegenerative disorders including Parkinsonrsquos disease and Alzheimerrsquos disease Mitochondria-targetedprotective compounds that prevent or minimize mitochondrial dysfunction constitute potential therapeutic strategies in theprevention and treatment of these central nervous system diseases This paper provides an overview of the involvement ofmitochondrial dysfunction in Parkinsonrsquos and Alzheimerrsquos diseases with particular attention to in vitro and in vivo studies onpromising endogenous and exogenous mitochondria-targeted protective compounds

1 Introduction

Mitochondria are spherical cytoplasmic organelles with asymbiotic origin that are present in all eukaryotic cellsStructurally mitochondria consist of two compositions andfunctionally different phospholipid membranes referred toas the outer membrane and the inner membrane and twoaqueous compartments the intermembrane space and themitochondrial matrix The outer membrane encloses theentire structure it has higher content in lipids (over 60)and it contains porins and a large multiprotein translocasecomplex allowing the passage to ions and larger moleculesThe inner membrane surrounds the mitochondrial matrixand it invaginates to form cristae that increase total surfacearea In addition the inner membrane has lipid content over20 and it is only permeable to small uncharged moleculesBoth membranes are separated by the aqueous compartmentintermembrane space located between them [1 2]Moreovermitochondria contain their own DNA (mDNA) held inthe mitochondrial matrix the human mDNA is a double-stranded circular genome made up of 16569 base pairs of

DNA that encodes 13 proteins 22 transfer RNAs (tRNAs) and2 ribosomal RNAs (rRNAs) [3] Functionally mitochondriaplay a vital role in regulating both metabolic and apoptoticsignaling pathwaysTheir main function is to produce energyas adenosine triphosphate (ATP) at the mitochondrial elec-tron transport chain (ETC) in the inner membrane throughthe cellular process of oxidative phosphorylation (OXPHOS)The mitochondrial ETC consists of four integral membraneoxidation-reduction electron and proton pump protein com-plexes (complex I NADHubiquinone oxidoreductase com-plex II succinate dehydrogenase complex III ubiquinone-cytochrome 119888 oxidoreductase complex IV cytochrome 119888oxidase) and an ATP synthase (complex V) which catalyzesADP conversion to form ATP [4] In addition mitochondriaparticipate in other series of functions including regulationof cellular calcium homeostasis balance between ROS pro-duction and detoxification (ie superoxide anion (O

2

∙minus) andthe highly reactive hydroxyl radical (∙OH)) mediation of theprocess of programmed cell death (apoptosis) and synthesisand metabolism of endogenous compounds such as steroidsheme groups and fatty acids [5]

Hindawi Publishing CorporationOxidative Medicine and Cellular LongevityVolume 2015 Article ID 408927 30 pageshttpdxdoiorg1011552015408927

2 Oxidative Medicine and Cellular Longevity

Consistent evidence suggests that mitochondrial failureis associated with early events in the pathogenesis of ageing-related neurodegenerative disorders including Parkinsonrsquosdisease and Alzheimerrsquos disease Mitochondria-targeted pro-tective compounds that prevent or minimize mitochondrialdysfunction constitute potential therapeutic strategies in theprevention and treatment of these central nervous systemdiseases [6 7] This paper provides an overview of theinvolvement ofmitochondrial dysfunction in Parkinsonrsquos andAlzheimerrsquos diseases with particular attention to in vitro andin vivo studies on promising endogenous and exogenousmitochondria-targeted protective compounds

2 Parkinsonrsquos Disease and Mitochondria-Targeted Protective Compounds

21 Parkinsonrsquos Disease (PD) Parkinsonrsquos disease is a chronicprogressive disorder characterized pathologically by the lossof dopaminergic neurons located in the substantia nigrapars compacta and to a lesser extent in putamen caudateand globus pallidus and by the formation of intracellularprotein inclusions of mainly alpha-synuclein (named asLewy bodies) in the remaining neurons [8 9] The firstclinical description was published in 1817 by the EnglishphysicianDr Parkinson in his work ldquoAn Essay on the ShakingPalsyrdquo [10] Parkinsonrsquos disease is the second most commonneurodegenerative disorder after Alzheimerrsquos disease whichaffects more than 63 million people over usually the ageof 60 worldwide Regarding epidemiology this age-relatedcentral nervous system disease appears to be slightly morecommon in whites than blacks and Asian people in menthan inwomen and in some geographical regions (ie ChinaIndia and USA) [11ndash13] The most relevant clinical featuresinclude tremor bradykinesia rigidity and dystonia howeverin addition to these characteristicmotor signs and symptomsneuropsychiatric and other nonmotor manifestations suchas depression cognitive impairment anxiety and psychosishave been also described [8 9 14] Although the exactcausal factors of Parkinsonrsquos disease remain unknown severalresearch studies point to specific genetic mutations andenvironmental factors [15 16] It has been estimated thataround 5ndash10 in every 100 people suffering from Parkinsonrsquosdisease are associated with gene mutations Scientifics haveidentified at least 13 gene mutations among which one couldhighlight those in the genes SNCA (synuclein alpha non-A4 component of amyloid precursor) PARK2 (Parkinsonrsquosdisease autosomal recessive juvenile 2) PARK7 (Parkinsonrsquosdisease autosomal recessive early-onset 7) PINK1 (PTEN-induced putative kinase 1) and LRRK2 (leucine-rich repeatkinase 2) [15]The SNCA gene encodes for the protein alpha-synuclein which is a key component of Lewy bodies thePARK2 gene encodes for the E3 ubiquitin ligase parkinwhich is implied in mitochondrial maintenance the PARK7gene encodes for the antioxidant protein DJ-1 PINK 1gene encodes for a serinethreonine-protein kinase with aprotective mitochondrial role Alterations of SNCA PARK2PARK7 and PINK1 genes are involved in the early-onsetParkinsonrsquos disease (this is diagnosed before being 50 years

old) [17ndash20]The LRRK2 gene which encodes for the proteindardarin has been associated with the late-onset Parkinsonrsquosdisease [21] The rest around 95 of diagnosed Parkinsonrsquosdisease cases are sporadic in which environmental factorssuch as pesticides and dietary factors among others seemto play a crucial role Researchers have identified severalcommon pesticides that their exposure may increase the riskof developing Parkinsonrsquos disease among which rotenoneparaquat dithiocarbamates (ie maneb ziram) pyrethroids(ie deltamethrin) organochlorine (dieldrin) imidazoles(ie triflumizole benomyl) and 22-dicarboximides (iefolpet aptan) are included [22 23] Regarding dietary factorsboth dietary patterns orand dietary nutrients that may pro-tect or may increase against to suffer from Parkinsonrsquos diseasehave been reported As an example in a case control studyperformed during ten years for establishing the influence ofminerals vitamins and fats in the etiology of Parkinsonrsquos dis-ease an association between a high intake of a combinationof iron and manganese and the development of Parkinsonrsquosdiseasewas found [24] On the other hand a large prospectivestudy performed over fifteen years with 49 692 men and81 676 women revealed that the high intake of fruit vegeta-bles legumes whole grains nuts fish and poultry the lowintake of saturated fat and the moderate intake of alcohol areprotective dietary patterns against Parkinsonrsquos disease [25]

211 Mitochondrial Dysfunction in Familial PD As we havepreviously commented around 5ndash10 of Parkinsonrsquos dis-ease cases involve gene products Mutations in ATP13A2(PARK9) DJ-1 (PARK7) parkin (PARK2) and PTEN-induced putative kinase 1 (PINK1) (PARK6) are associatedwith autosomal recessive PD and mutations in 120572-synucleingene and leucine-rich repeat kinase 2 gene (LRRK2) areimplicated in autosomal dominant PD (see Figure 1) [16]

Mutations in the ATP13A2 gene (PARK9) encodingfor a lysosomal type 5P-type ATPase cause a hereditaryrare juvenile onset autosomal recessive Parkinsonism withdementia named as Kufor-Rakeb syndrome This particularParkinsonrsquos form characterized by supranuclear gaze palsydystonia pyramidal signs and cognitive impairment wasfirst evidenced in 2006 in members of a nonconsanguineousChilean family The neuronal damage associated with muta-tions in this gene is related to alterations inmitochondria andlysosomes functions and divalent cation regulation [26ndash28]

DJ-1 mutations on chromosome 1p36 cause autosomalrecessive early-onset PD and its pathological mechanismseems to be linked with mitochondrial fragmentation andmitochondrial structural damage and consequently defects inthe mitochondrial function of dopaminergic cells [29 30]

Mutations in the parkin gene product which is an ubiqui-tin ligase lead to an early-onset familial Parkinsonrsquos diseaseand its first description dates in the year 1998 Experimentalstudies have determined that the pathology of parkin isassociated with alterations in the mitochondrial recogni-tion transportation and ubiquitination and with mitophagyimpairment [31 32]

Mutations in themitochondrial serinethreonine-proteinkinase PINK1 result in alterations in the mitochondrial

Oxidative Medicine and Cellular Longevity 3

III

IIIIV

V

Alpha-synuclein

PINK1

ATP production

PINK1

ROS

PINK1

Parkin

Mitochondrialpotential

LRRK2

LRRK2

Mitochondrialdysfunction

DJ-1

DJ-1

DJ-1

Figure 1 The role of gene products in Parkinsonrsquos disease

morphology and function (defects in complex I activity)and they are strongly associated with a form of autosomalrecessive early-onset Parkinsonrsquos disease [33 34]

Mutations in the protein 120572-synuclein which is the maincomponent of Lewy bodies (it represents 1 of total cytosolicprotein of brain cells) have been reported to play a keyrole in the pathogenesis of autosomal dominant early-onsetParkinsonrsquos disease Particularly two mutations in the alpha-synuclein gene (A30P and A53T) have been identified whichlead to the formation of pathogenic pore-like annular andtubular protofibrils These mutations inhibit the activity ofcomplex I and induce mitochondrial fragmentation causingmitochondrial dysfunction [35 36]

Mutations in the gene encoding leucine-rich repeatkinase 2 (LRRK2) are related to autosomal dominant Parkin-sonrsquos disease form The most common mutation is G2019Sthat accounts for 5-6 of familial cases of Parkinsonrsquos diseaseExperimental studies have identified different pathogenicmechanisms for altered LRRK2 that involve inflammationprocesses oxidative stress and mitochondrial dysfunctionamong others Focusing on this last pathogenic mechanismmutations in LRRK2 cause mitochondrial fragmentation anda downregulation in mitochondrial homeostasis (reductionin mitochondrial membrane potential and ATP production)[37 38]

212 Mitochondrial Dysfunction in Sporadic PD Around95 of diagnosed Parkinsonrsquos disease cases are sporadicOne of the proposed mechanisms for the dopaminergicneurons degeneration in sporadic Parkinsonrsquos disease cases isrelated to an excessive production of reactive oxygen species(ROS) that leads to oxidative stress situation An excess of

ROS causes the oxidative modification of macromolecules(lipids proteins and DNA) leading to cell damage andeven cell death The pathological effect of ROS is alsoinvolved in a reduction of ATP (adenosine triphosphate)production in an increase of iron levels and in an increaseof intracellular calcium levels and alterations in mitochon-drial respiratory chain complexes function In addition tooxidative stress mechanism protein misfolding aggregationand deposition have been reported as other common patho-logical mechanisms in Parkinsonrsquos disease A dysfunction inthe ubiquitin-proteasome-system (UPS) and the autophagy-lysosomal pathway (ALP) as evidenced in a reduction ofproteasome and autophagy activities and in postmortembrains of patients suffering from this neurodegenerativedisease has been demonstrated [39ndash43]

213 PostmortemPDBrain Tissues ExperimentalModels andCell-Based Models Many evidences from postmortem PDbrain tissues experimental models and cell-based modelshave demonstrated the involvement of mitochondria dys-function in the pathogenesis of both familial and sporadicParkinsonrsquos disease

The first evidence of the relationship between mitochon-dria and Parkinsonrsquos disease dates from the second half ofthe twentieth century when the postmortem brain analysisof some drug abusers of intravenous 1-methyl-4-phenyl-1236-tetrahydropyridine (MPTP) who have developed aprogressive and irreversible parkinsonism revealed a signifi-cant nigrostriatal degeneration MPTP easily passes throughthe blood-brain barrier it is oxidized and transformed into1-methyl-4-phenylpyridinium (MPP+) and within neurons


MPP+ inhibits the complex I (NADH-quinone oxidore-ductase) of the electron transport chain resulting in anenhanced reactive oxygen species (ROS) generation (iehydroxyl radicals superoxide anion radical) and a decrease inenergy supply (ATP production) [44]Many lines of evidencehave further demonstrated complex I deficiency or impair-ment in the cortical brain tissue frontal cortex striatumskeletal muscle and platelets of patients with Parkinsonrsquosdisease [40 45 46] In addition to complex I other studieshave reported that a deficiency in the activity of complexII (succinate ubiquinone oxidoreductase) and complex III(ubiquinol-cytochrome C oxidoreductase) is also associatedwith the pathogenesis of Parkinsonrsquos disease Complex IIIinhibition as what happens with complex I causes an over-production of ROS leading to oxidation of lipids proteinsand DNA and it finally triggers to cell death [47 48] More-over ROS mediates the mitochondrial-dependent apoptosisby inducing mitochondrial permeability transition releasingof cytochrome c activation of caspase-3 and caspase-9translocation of Bax to mitochondria and the activation ofc-Jun N-terminal kinase (JNK) and p38 mitogen-activatedprotein kinase (p38 MAPK) in the cytosol [49 50]

The neurotransmitter dopamine has been also relatedto the pathogenesis of Parkinsonrsquos disease In vitro experi-mental researches on neuronal cell types and isolated brainmitochondria and in vivo studies using different animalmodels and postmortem brain studies in Parkinsonrsquos diseasehave demonstrated that dopamine oxidation and reactivedopamine quinone oxidation products inducemitochondrialrespiration uncoupling and cause ATP levels reduction andinactivate proteasomal activity among other effects whichcontribute to mitochondrial dysfunction [51ndash57] The roleof tetrahydrobiopterin (BH4) in Parkinsonrsquos disease etiologyis also remarkable BH4 is an obligatory cofactor for thedopamine synthesis enzyme tyrosine hydroxylase and it ispresent selectively in monoaminergic neurons in the brainIt has been suggested as an endogenous molecule thatcontributes to the dopaminergic neurodegeneration throughan inhibition of the activities of complexes I and IV of theelectron transport chain (ETC) together with a release ofmitochondrial cytochrome C and a reduction of mitochon-drial membrane potential [58]

There are other studies which involve calcium excitotoxi-city and nonexcitotoxicity relatedmechanisms in the etiologyof Parkinsonrsquos disease Alterations in calcium influx in neu-rons via L-type voltage-dependent channels and N-methyl-D-aspartate (NMDA) receptors may lead to an excitotoxiccellular calcium accumulation that can cause mitochon-drial dysfunction by reducing ATP production activatingmitochondrial permeability transition increasing ROS gen-eration and inducing mitochondrial-dependent apoptosis[59 60] Other circumstances not ordinarily toxic havebeen reported to contribute to mitochondrial dysfunctionHence Sheehan et al (1997) showed using mitochondriallytransformed cells (cybrids) that the capacity to sequestratecalciumwas lower in patients with Parkinsonrsquos disease than incontrol subjects suggesting that this homeostasis alterationcould increase neurons cell death [61]

Regarding familial Parkinsonrsquos disease mutations in sev-eral genes previously reported (Parkin PINK1 DJ-1 120572-synu-clein and LRRK2) which encode for mitochondrial proteinshave been identified to contribute to mitochondrial dysfunc-tion [62 63]

There are different neurotoxins including rotenone 1-methyl-1236-tetrahydropyridine (MPTP) 6-hydroxydop-amine (6-OHDA) and paraquat among others which havebeen extensively used as Parkinsonrsquos disease experimentalmodels to mimic the neuropathology of this neurodegener-ative disorder in both in vitro (ie human neuroblastomaSK-N-SH cells) and in vivo (animals models such as ratsmice) investigations and consequently to help establishneuroprotective strategies Rotenone an insecticide extractedfrom the roots of Derris spp and Lonchocarpus spp (Legu-minosae family) acts by inhibiting the mitochondrial res-piratory chain complex I [64] Paraquat (11-dimethyl-441015840-bipyridinium dichloride) which is a quaternary nitrogenherbicide used to control weed growth has been reported toincrease ROS generation and induce120572-synuclein fibril forma-tion [65] The 1-methyl-1236-tetrahydropyridine (MPTP)a byproduct obtained during the chemical synthesis of ameperidine analog is metabolized in the brain to the toxiccompound MPP+ which inhibits complex I of the electrontransport chain [44] The catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) via intracerebral infusioncauses the irreversible loss of nigrostriatal dopaminergicneurons by inducing ROS production and inhibiting complexI and complex IV of the electron transport chain [66]

22 Mitochondria-Targeted Protective Compounds in PDEndogenous and exogenous compounds are in continuinginvestigation as mitochondria-targeted agents to prevent ortreat Parkinsonrsquos disease (Figure 2) Table 1 reports com-pounds that have been demonstrated to be promising agentsin the protection of mitochondrial dysfunction in differentParkinsonrsquos disease models Hence among the endogenouscompounds investigated so far the hormone melatonin theneuropeptide cocaine and amphetamine regulated transcript(CART) the ursodeoxycholic acid the mitoQ (mitoquinonemesylate) and the 120572-lipoic acid can be highlighted Thehormone melatonin has been shown to exert in vivo mito-chondrial protective action in MPTP-induced mice model6-OHDA rat model and rotenone-induced rat model bymaintaining mitochondrial membrane potential increasingantioxidant enzymatic (ie SOD CAT) and nonenzymaticlevels (ie glutathione) inhibiting ROS overproductionincreasing ATP production decreasing calcium concentra-tion levels and enhancing mitochondrial complex I activ-ity [67ndash71] The neuropeptide cocaine and amphetamineregulated transcript (CART) protected mitochondrial DNAand cellular proteins and lipids of human neuroblastomaSH-SY5Y cells HEK293 cells and cultures of cortical andhippocampal neurons exposed to hydrogen peroxide [72]The ursodeoxycholic acid (one of the secondary bile acids)and the mitoQ (mitoquinone mesylate) acted as antiapop-totic agent in human neuroblastoma SH-SY5Y cells treatedwith SNP and 6-OHDA respectively [73 74] The 120572-lipoic


III

IIIIV

V

Mitochondrial DNA

DNA damage

Apoptosis

Green tea polyphenols melatonin

Mitochondrial

Mitochondrial

permeabilitytransition pore (MPTP)

membrane potentialMelatonin lycopene

respiratory chain

Hesperidin quercetin 120572-lipoic acidxyloketal B melatonin

Neuropeptide cocaine amphetamineregulated transcript (CART)

Chunghyuldan curcumin hesperidin green teapolyphenols pyruvate quercetin 120572-lipoic acidxyloketal B melatonin rosmarinic acid harmalolharmine lycopene glutamoyl diester of curcumin

Chunghyuldan curcumin pyruvate silymarinbaicalein tyrosol hesperidin green tea polyphenolsquercetin 120572-lipoic acid xyloketal B melatoninrosmarinic acid harmalol harmine glutamoyldiester of curcumin

Ursodeoxycholic acid licorice Panax ginsengMitoQ (mitoquinone mesylate) caffeic acid phenethyl estersalvianic acid A salvianolic acid B protocatechuic acidumbelliferone esculetin osthole Chunghyuldan curcuminsilymarin baicalein tyrosol hesperidin green tea polyphenolspyruvate isoborneol piperine tetramethylpyrazine astaxanthin

uarr ROS

uarr ROSdarr Mitochondrial

darr ATP production

Ca2+

uarr Mitochondrial Ca2+

uarr Cytosolic Ca2+

darr Antioxidant system

Figure 2 Mechanisms of mitochondrial dysfunction and mitochondria-targeted drugs that have produced beneficial effect in PD models

acid has been evaluated as mitochondrial-targeted protec-tive compound in several in vitro and in vivo Parkinsonrsquosdisease models (ie PC12 cells SK-N-MC cells and ratmodel toxins as MPP(+) and rotenone) this organosulfurcompound derived fromoctanoic acid protectsmitochondriaby inhibiting ROS production increasing glutathione levelsandmaintainingmitochondrialmembrane potential [75ndash78]Pyruvate has also been demonstrated in in vitro studies thatmaintains mitochondrial membrane potential and inhibitsROS generation and nuclear translocation of NF-kappaB aswell as mitochondrial apoptotic pathway [79 80]

Several natural products from medicinal plants bothisolated compounds and extracts have been demonstrated inin vitro and in vivo studies to exert promising mitochondrialprotection As extracts it has been reported that berries richin anthocyanidins and proanthocyanidins protect mitochon-dria from rotenone-induced changes in the respiratory chain[118] The silymarin which is a standardized extract of themilk thistle seeds maintained mitochondrial integrity andfunction and inhibited mitochondrial apoptotic pathway inMPP(+)-induced ratmodel [119] Green tea polyphenols havebeen also evidenced to inhibit mitochondrial apoptotic path-way (increasing Bcl2 and decreasing caspase-3 activity) andto maintain mitochondrial membrane potential to inhibitROS production and calcium concentration levels [120] Thelicorice (root of Glycyrrhiza glabra) inhibited dopaminergicapoptotic cell death as evidenced in the increase in Bcl2levels and in the decrease in Bax levels caspase-3 activitycytochrome c release and JNK andMAP activities in amodelof 6-OHDA-induced Parkinsonrsquos disease [121] The waterextract of Panax ginseng also inhibited apoptosis MPP(+)-induced in the human neuroblastoma SH-SY5Y cells bydecreasing Bax levels caspase-3 activity and cytochromerelease and increasing Bcl2 levels [122]

The herbal medicine Chunghyuldan inhibited caspase-3ROS generation and maintained mitochondrial membranepotential in 6-OH Parkinsonrsquos disease model [123] Amongisolated natural products highlight those with polyphenolstructureThe polyphenol resveratrol has been demonstratedin in vitro primary fibroblasts cultures from patients withparkin mutations (PARK2) to regulate mitochondrial energyhomeostasis as evidenced in the increment of complex Iactivity citrate synthase activity basal oxygen consumptionand ATP production and in the decrement of lactate content[111] The polyphenol hesperidin inhibited mitochondrialapoptotic pathway (increased Bcl2 levels and decreased Baxcaspase-3 and caspase-9 activities and inhibited cytochromec release) maintained mitochondrial membrane potentialinhibited ROS production and increased glutathione levelsin in vitro human neuroblastoma SK-N-SH cells model ofrotenone-induced Parkinsonrsquos disease [98] Quercetin res-cued toxic-induced defects in mitochondria in in vitro andin vivo experiments Quercetin inhibited ROS generation andmaintained mitochondria membrane potential in rotenone-induced rat model [108] Moreover quercetin decreased theproduction of superoxide radicals and inhibited the expres-sion of the inducible nitric oxide synthase protein expressionin in vitro glial-neuronal system model of MPP(+)-inducedParkinsonrsquos disease [109] The flavonoid baicalein inhibitedin vitro apoptotic mitochondrial cell death and maintainedmitochondrial integrity and function in both SH-SYTY andPC12 cells in 6-OHDA and rotenone Parkinsonrsquos diseasemodels as evidenced in the decrease in caspase-3 caspase-7 caspase-9 and JNK activities and in the maintenanceof mitochondrial membrane potential increment of ATPcontent and reduction of ROS production [82ndash84] Thetyrosol protected CATHa cells against MPP(+)-toxicity byinhibiting apoptotic cell death via activation of PI3KAkt


Table1Parkinsonrsquos

diseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Acetyl-L-carnitin

eQuaternary

ammon

ium

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon

drialintegrityandfunctio

nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[65]

Astaxanthin

Non

provitamin

Acaroteno

id

MPP

(+)-indu

cedmou

semod

elIn

vitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

MPP

+-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xand120572-synuclein

darrcaspase-3

[81]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lmaintainmito

chon

drialredox

activ

ity[82]

Baicalein

Flavon

oid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

eland

isolatedratb

rain

mito

chon

driaof

roteno

neindu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3andcaspase-7

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrintracellularA

TPprod

uctio

n

[83]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lInhibitio

nof

them

itochon

drialapo

ptoticpathway


darrp-c-JunN-te

rminalkinase

(JNK)

[84]

Caffeicacid

phenethyleste

rPh

enoliccompo

und

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


n

[85]

Prim

arycultu

reso

fcerebellarg

ranu

leneuron

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

darrcytochromec

release

[86]

CNB-001

Pyrazolederiv

ativeo

fcurcum

in

MPT

P-indu

cedrodent

PDmod

elMaintenance

ofno

rmalmito

chon

drialm

orph

olog

yandsiz

e[87]

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3andcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

l

[88]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Curcum

inPo

lyph

enol

PC12

cells

mutantA

53T120572-synuclein-in

ducedcelldeath

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n

[89]

Mou

sebrainandthe1RB

3AN27

(N27)ratdo

paminergic

neuron

alcelllin

emod

elof

buthionine

sulfo

ximine-indu

cedPD

Maintenance

ofmito

chon


nuarractiv

ities

ofcomplex

Idarroxidatived

amagetoproteins

uarrglutathion

e

[90]

DL-3-n-

butylphthalid

e(N

BP)

Synthetic

compo

und

basedon

L-3-n-bu

tylphthalid

e

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[91]

Echinacosid

ePh

enylethano

idglycoside

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

H2O

2-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

[92]

Edaravon

ePy

razolederiv

ative

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xMaintenance

ofmito

chon


ndarrRO

Sgeneratio

n

[93]

Esculetin

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ginseno

sideR

ePanaxatriolsapon

inPINK1

nullcells

Reversingthed

eficitincomplex

IVactiv

ity

uarrLR

PPRC

Hsp90and

Hsp60

levels

[95]

Glutamoyld

ieste

rof

curcum

inPo

lyph

enol

Mou

sebrainmito

chon

driaindu

ced-peroxynitrite

PDMaintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[96]

Harmalol

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Harmine

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Hesperid

inPo

lyph

enol

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[98]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Isob

orneol

Mon

oterpeno

idalcoho

lIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[99]

Kaem

pferol

Flavon

oid

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

eland

prim

aryneuron

sofrotenon

e-indu

cedPD

uarrAu

toph

agy

[100]

120572-Lipoica

cid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[75]

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[76]

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[77]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

PD

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[78]

Lycopene

Caroteno

id

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrlip

idperoxidatio

nuarrintracellularA

TPprod

uctio

nuarrmito

chon

drialD

NAcopy

numbersandmito

chon

drialR

NA

transcrip

tlevels

[101]

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

Dactiv

ityuarrglutathion

e

[102]

MPT

P-indu

cedmiceP

Dmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

luarrantio

xidant

enzymelevels

uarrintracellularA

TPprod

uctio

n

[67]

Roteno

ne-in

ducedratP

Dmod

el

Maintenance

ofmito

chon


ndarrRO

Sgeneratio

nuarrglutathion

euarrSO

Dandcatalase

activ

ities

[68]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Melaton

inHormon

eRo

teno

ne-in

ducediso

latedratb

rain

mito

chon

driaPD

mod

elMaintenance

ofmito

chon


ndarrCa

2+levels

darrRO

Sgeneratio

n[69]

6-OHDA-

indu

cedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[70]

MPP

(+)-indu

cediso

latedratliver

mito

chon

driaandstr

iatal

synaptosom

esPD

mod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[71]

Mito

Q(m

itoqu

inon

emesylate)

mdashIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xdarrDrp1

[73]

N-Acetylcysteine

Aminoacid

deriv

ativeH

2O2andtoxicq

uino

nesd

erived

from

dopamine-indu

cedrat

PDmod

el

Maintenance

ofmito

chon


nuarrmito

chon

drialrespiratory

activ

ityuarrNa+

K+-AT

Pase

activ

ity[103]

Neuropeptidec

ocaine

andam

phetam

ine

regu

latedtranscrip

t(C

ART

)

Peptide

Invitro

human

neurob

lasto

maS

H-SY5

YHEK

293cellsand

cultu

reso

fcortic

alandhipp

ocam

paln

eurons

ofH

2O2-indu

ced

PD

Maintenance

ofmito

chon


nprotectio

nof

mito

chon

drialD

NA(m

tDNA)cellu

larp

roteins

andlip

ids

[78]

Osth

ole

Cou

marin

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[104]

Piperin

eAlkaloid

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

[105]

Polyhydroxylated

fullerene

deriv

ative

C(60)(OH)(24)

mdashIn

vitro

human

neurob

lasto

mac

ellsmod

elof

MPP

(+)-indu

ced

PD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarractiv

ities

ofcomplexes

Iand

IIdarroxidatived

amagetoDNAandproteins

[106]

Protocatechu

icacid

Polyph

enol

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrcaspase-3

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[107]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Pyruvate

Organicacid

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

H2O

2-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[79]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

dopamine-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrp53

darrnu

clear

translo

catio

nof

NF-kapp

aBInhibitio

nof

them

itochon

drialapo

ptoticpathway

[80]

Quercetin

Biofl

avon

oid

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


ndarrRO

Sgeneratio

nmaintainmito

chon

drialm

embranep

otentia

l[108]

Invitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[109]

Rapamycin

Macrolid

e6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

DandGSH

-PX

[110]

Resveratrol

Polyph

enol

Invitro

prim

aryfib

roblastscultu

resfrom

patie

ntsw

ithparkin

mutations

(PARK

2)

Maintenance

ofmito

chon


nuarrcomplex

Iactivity

uarrcitrates

ynthasea

ctivity

uarrbasaloxygenconsum

ption

uarrmito

chon

drialA

TPprod

uctio

ndarrlactatec

ontent

[111]

Rosm

arinicacid

Polyph

enol

Invitro

MES

235do

paminergicc

ellsmod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[112]

Salvianica

cidA

Polyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

x[113]

Salviano

licacid

BPo

lyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[114]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Sesamin

Lign

anIn

vitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[22]

Tetram

ethylpyrazine

Pyrazine

MPT

P-indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[115]

Tyrosol

Phenoliccompo

und

MPP

(+)-indu

cedCA

THacells

PDmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lmaintainintracellularA

TPprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

(i)activ

ationof

PI3K

Akt

signalling

pathway

[116]

Umbelliferone

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ursod

eoxycholic

acid

Second

arybileacids

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

SNP-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3caspase-7andcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[74]

XyloketalB

Triterpenoid

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

eland

Caenorhabditiseleg

anso

fMPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[117]


signaling pathway and by maintaining ATP production andmitochondria membrane potential [116] The caffeic acidphenethyl ester inhibited 6-OHDA-induced mitochondrialapoptotic pathway in in vitro and in vivomodels [85 86]Thecurcumin polyphenol derived from the spice turmeric acts asmitochondrial antiapoptotic agent through the inhibition ofcaspase-3 and caspase-9 activities and cytochrome c releaseand it also protects mitochondrial integrity and function viaROS production inhibition and complex I activity enhance-ment [89 90] In addition to curcumin its synthetic pyra-zole derivative compound CNB-001 has been also studiedwhich avoids rotenone-inducedmitochondrial damage in thehuman neuroblastoma SK-N-SH cells by inhibiting mito-chondrial apoptotic pathway and maintaining mitochondrialstructure [87 88] Glutamoyl diester of curcumin has alsobeen shown to maintain mitochondrial membrane potentialand to inhibit ROS production in mouse brain mitochon-dria induced-peroxynitrite Parkinsonrsquos disease model [96]Salvianic acid A and salvianolic acid B isolated from Salviaspp as well as protocatechuic acid afford in vitro protectionthrough antiapoptotic pathway [107 113 114] The flavonoidkaempferol exerts antiparkinsonian effect via autophagy[100] and rosmarinic acid maintains mitochondria protec-tion by maintaining mitochondrial membrane potential anddecreasing ROS production [112]

Other natural products with mitochondrial protectiveeffect are the coumarins umbelliferone esculetin and ostholewhich in in vitro and in vivo Parkinsonrsquos disease modelshave been demonstrated to possess antiapoptotic propertieson mitochondria [94 104] Other compounds that exertprotection via inhibition of the mitochondrial apoptoticpathway are the monoterpenoid alcohol isoborneol [99]the alkaloid piperine [105] the pyrazine tetramethylpyrazine[81] and the nonprovitamin A carotenoid astaxanthin [115]On the other hand the 120573-carboline alkaloids harmalol andharmine maintained mitochondria membrane potential anddecreased ROS generation in PC12 cells exposed to S-nitroso-N-acetyl-DL-penicillamine (SNAP) [97] Moreoverthe triterpenoid xyloketal B also maintained mitochon-dria membrane potential and decreased ROS generationand it increased glutathione levels in in vitro rat adrenalpheochromocytoma (PC12) cells and Caenorhabditis elegansof MPP(+)-induced PD [117] Furthermore the carotenoidlycopene inhibited macromolecular mitochondrial damage(lipids DNA and proteins) overproduction of ROS ATPfailed production and cytochrome c release in MPP(+)-induced human neuroblastoma SK-N-SH cells and rotenone-induced rat model [101 102]

3 Alzheimerrsquos Disease and Mitochondrial-Targeted Protective Compounds

31 Alzheimerrsquos Disease Alzheimerrsquos disease (AD) is a neu-rodegenerative disease characterized by progressive cognitivedecline leading to complete need for care within several yearsafter clinical diagnosis [124] AD is the most common formof dementia being the most prevalent neurodegenerativedisease (followed by Parkinsonrsquos disease) and accounts for

approximately 65 to 75 of all dementia cases It has beenestimated that Alzheimerrsquos disease affects over 44 millionpeople worldwide mainly after the age of 65 years [125 126]The incidence of AD augments with age in an exponentialmanner and its prevalence increases from 3 among indi-viduals aged 65ndash74 to almost 50 among those 85 or olderthese numbers can be translated to the extremely high healthcare costs thatAD represents [127] In addition because of theaging of the population it is expected that the prevalence willquadruple by 2050 which means 1 in 85 persons worldwidewill be living with the disease [128]

AD is a progressive neurodegenerative disease with amarked late onset (late diagnosis as well) and mainly charac-terized by progressive decline of cognitive functions mem-ory and changes in behavior and personality [129 130]The two major pathophysiological hallmarks that have beenobserved in postmortem brains of AD patients include extra-cellular 120573-amyloid protein (A120573) deposits in the form of senileplaques and intracellular deposition of the microtubule-associated protein tau as neurofibrillary tangles especiallyabundant in the regions of the brain responsible for learningand memory These features have been linked to an abnor-mally enhanced neuronal loss in this condition especiallyaffecting cholinergic neurons and consequently leading to areduction in the levels of the neurotransmitter acetylcholinein the hippocampus and cortex areas of brains of ADpatients Moreover AD has also been associated with theloss of synapses synaptic function inflammatory responsesinvolving glial cells and mitochondrial abnormalities [131ndash133]

Considering AD pathogenesis multiple etiological fac-tors including genetics environmental factors diet andgeneral lifestyles have to be taken into account [134] Most ofthe cases of AD are believed to be ldquosporadicrdquo and their causalfactors are still unknown for the vast majority of patientson the other hand genetic factors cause about 2 of all ADcases and include mutations in APP (A120573 protein precursor)presenilin-1 and presenilin-2 genes and polymorphisms inapolipoprotein allele E4 [135 136]

Due to the complex and not fully understood etiopathol-ogy of AD no available drug has been shown to completelyprotect neurons in AD patients and there is a continuoussearch for new compounds and therapeutic tools Thereare two possible conceptual approaches to the treatment ofAD The first one is a symptomatic treatment that tries tominimize tertiary cognitive symptoms and protects fromfurther cognitive decline it is the most common therapeutictendency and drugs such as tacrine donepezil and rivastig-mine have been used with this purpose with limited efficacyAnother approach is the treatment addressed to prevent theonset of the disease by sequestering the primary progenitorsor targets to reduce the secondary pathologies of the diseaseto slow disease progression or to delay onset of disease bypreventing or attenuating neuronal damaging factors [137138] With regard to this compounds that exert activityagainst oxidative stress andmitochondrial dysfunction inAD(as discussed below) deserve to be considered as potentialtherapeutic options


During the last two decades consistent evidences haveproposed oxidative stress as a crucial pathogenic mechanismunderlying AD [139] Oxidative stress (OS) occurs whenthe production of reactive oxygen species (ROS) exceedsthe antioxidant enzymatic and nonenzymatic cellular mech-anisms Actually the 120573-amyloid peptide A120573

1ndash42 (insolubleform) which forms the senile plaques exerts neurotoxicityinvolving OS in AD Particularly this A120573

1ndash42 has the abilityto produce ROS mainly hydrogen peroxide when it reactswith transition metal ions present in senile plaques [140]As a result of OS accumulated oxidative damage to lipidsproteins and nucleic acids in postmortem studies of brainsof patients with AD has been identified advanced glycationend-products (AGEs) advanced lipid peroxidation end-products nucleic acid oxidation carbonyl-modified neuro-filament protein and free carbonyls [141] The brain ismore susceptible to OS than other organs because of a lowantioxidative protection system which allows for increasedexposure of target molecules to ROS the higher level of ROStogether with neuroinflammation and excessive glutamatelevels is proposed to contribute to neuronal damage anddeath in AD [142]

311Mitochondrial Dysfunction inAD Mitochondria are theprimary source of ROS and oxidative damage to mitochon-drial components precedes damage to any other cellular com-ponent during the development of neurodegenerative dis-eases [143] Actually mitochondrial dysfunction has largelybeen demonstrated as one of the main key cytopathologiesof AD [144 145] Numerous evidences suggest the involve-ment of 120573-amyloid protein deposits in the mitochondrialdysfunction found in AD as a plausible mechanism for itsneurodegenerative effects [146ndash148] In support of this it hasbeen shown that cells depleted of endogenousmDNA lackingfunctional electron transport chains (ETC) are resistant toA120573 toxicity [149] also a reduced respiratory capacity andlow cytochrome oxidase activity were found in isolatedmitochondria exposed to A120573 [150 151] transgenic miceexpressing mutant APP (amyloid protein precursor) genesexhibit mitochondrial dysfunction and an AD transgenicmouse line presents early expression of genes encodingmito-chondrial proteins and ETC subunits as an initial cellularchange in AD pathology [152]

Mitochondria have been shown to be a direct site ofA120573 accumulation in AD neurons and various experimentalmodels of AD were used by researchers to verify the effectof that specific accumulation on cell death [153] ActuallyManczak et al proved an association between mutant APPderivatives (A120573 monomers and oligomers such as A120573

1ndash40and A120573

1ndash42) and mitochondria in cerebral cortex slices fromTg2576 mice and N2a cells expressing mutant APP Suchaccumulation supposes an increase in mitochondrial ROSproduction together with a reduced Cyt C oxidase activitythus relating in vivo oxidative stress and impaired mitochon-drial metabolism to the toxic effects of A120573 peptides [154]Further Devi et al demonstrated that the mitochondrialdysfunction in human AD brain is associated with theabnormal accumulation of APP across the mitochondrial

import channels In postmortem evaluations it was evidencedthat nonglycosylated full-length and C-terminal truncatedAPP had been accumulated exclusively in the protein importchannel of mitochondria of AD brains (specially higheraccumulation in AD-vulnerable regions such as cortexhippocampus and amygdala) by forming stable complexeswith the outer membrane translocase andor the inner mem-brane translocase the effect of such association could inhibitthe entry of nuclear encoded Cyt C oxidase protein thusdiminishing its activity in mitochondria and increasing thelevels of H

2O2The higher the level of arrestedmitochondrial

APP the worse the mitochondrial dysfunction [155]What ismore a recent study indicated thatmitochondria-

targeted A1205731ndash42 accumulation is the necessary and sufficient

condition for A120573-mediated mitochondrial impairments andderived cellular death In an in vitromodel ofmice hippocam-pal cell line (HT22 cells) an exogenous A120573

1ndash42 treatmentcaused a deleterious alteration in mitochondrial morphologyand function which was blocked by a clathrin-mediatedendocytosis blocker besides specific mitochondria-targetedaccumulation of A120573

1ndash42 in HT22 cells using a mitochondria-targeting sequence reproduced the same morphological andfunctional alterations of mitochondria as those observed inAPP mutant mice model and the previous A120573

1ndash42-treatedHT22 cells Mitochondria-mediated apoptotic cell deathwas observed in both models thus implying that no othersignaling alteration induced by A120573 plays a more relevant rolein cell death than its mitochondrial toxicity [156]

In general mitochondrial dysfunction in AD is essen-tially characterized by diminution in complex IV activity(cytochrome c oxidase) decline in other enzymes of tricar-boxylic acids cycle andmutations tomDNAThemechanismthat underlies the complex IV defect is not clearly knownbut a study on SK-N-SH cells exposed to A120573-inducedtoxicity showed a decrease in mDNA encoded complexIV subunits at both the mRNA and protein levels thisfinding suggests a possible relationship between decreasedcomplex IV activity and mDNA perturbation [157] Resultsfrom cybrids studies also imply that AD is characterizedby specific mDNA mutations that correlate with defects incertain mitochondrial respiratory complexes These changesgenerate an increased production of oxidant species and freeradicals such as hydrogen peroxide In turn a deficiencyin energy metabolism and ATP generation is a seriousconsequence of impaired mitochondrial function [158 159]In addition deficiency in scavenging mitochondrial freeradicals may similarly contribute to the excessive oxidativedamage in the affected brain regions in AD For instancedecreased mitochondrial MnSOD expression level has beenfound in AD patients as well as decreased Coenzyme Qin peripheral tissues and brains [160 161] Therefore arelationship between the mitochondrial dysfunction and theoxidative stress situation is established

Neurodegeneration and synaptic degradation in AD areprimarily mediated by defective mitochondrial biogenesisand axonal transport of mitochondria [162] Normal mito-chondrial dynamics an essential function inmaintaining cellviability is likewise impaired in AD Disturbances affectingthe balance of fusion and fission processes trigger serious


mitochondrial changes and lead to cellular perturbationssuch as apoptosis Recent studies have found altered levelsof mitochondrial fusion (including MNF-12 and OPA1) andfission (FIS1) proteins in AD hippocampal tissues meaningdecreased fusion and increased fission processes mitochon-drial fission proteinDLP1 has also been found to be decreasedin hippocampal neurons [163] Moreover mitochondrial cal-cium overload is another feature of mitochondrial dysfunc-tion inADA120573has been shown to cause calciumoverload thatthen causes increased free radical accumulation and provokesthe formation of mitochondrial transition pore (mPTP) thusleading to exacerbation of cytoplasmic calcium and eventualneuronal death [164]

Further mitochondria play a pivotal role in aging andsenescence contributing to neural dysfunction with ageThey are actually the main cellular organelle implicated inthe process of neuronal apoptosis which takes place in anexcessive manner in AD brains [165] The fact that manyneurons undergo apoptosis in AD is evidenced by the pres-ence of high levels of activated proapoptotic proteins suchas caspase-3 and Bax in neurons that exhibit neurofibrillarytangle pathology [166]

Concerning AD models of study unfortunately there isno animal model so far that replicates all the major aspectsof AD pathology and symptoms andmodels based on postu-lated disease pathways are widely used to explore biologicaltargets [167] Regarding the investigation of the effects ofcompounds onmitochondrial dysfunction rodent transgenicmodels are very common for reproducing the mitochon-driopathy features in AD For instance an APP (amyloidprecursor protein) mice transgenic model demonstratedan accelerated upregulation of the apoptotic-related factorsinvolved in mitochondria-mediated apoptosis such as Baxand caspase-3 [168] Similarly isolated mitochondria fromAPPSW mice (expressing the Swedish familial mutation inAPP gene) presented an abnormally reduced mitochondrialrespiratory rate mitochondrial membrane potential (MMP)disruption increased ROS generation and lower ATP levels[169] APPPS1 transgenic mice include mutations both inAPP and in presenilin-1 genes and show similar mitochon-drial characteristics [170] Other models even express moremutations such as 3xTg-ADmousemodel that includes threemutant human genes APPswe presenilin-1 (PS1M146V) andtau protein (tau P301L) in this model MMP loss and highercaspases 3 and 9 activations are observed [171]

However most of the works assessing mitochondrialdefects in AD are still performed on toxin-induced invitro models With this respect rat primary neurons inculture exposed to A120573

1ndash42 oligomers reproduced the gen-eration of mPTP in mitochondrial membrane with sub-sequent calcium overload the MMP loss and release ofcytochrome C thus leading to cell death via mitochondrial-mediated apoptosis [172] Mouse neuroblastoma N2a cellscotransfected with Swedish mutant APP and Δ9 deletedpresenilin-1 (N2aSweΔ9) recapitulated similar loss of mito-chondrial integrity and function and evidenced increasedmitochondrial apoptotic pathway with a higher BaxBcl2ratio and augmented caspase-3 activity [173] Recent studieshave employed cybrid neurons resulting from incorporating

platelet mitochondria from AD patients into mitochondrialDNA-depleted neuronal cells (SH-SY5Y cell line) this modeldemonstrates changes in length and density of mitochon-dria imbalanced mitochondrial fission and fusion dynamics(altered expression and distribution of DLP1 and Mfn2proteins) together with reduced mitochondrial function andenergy metabolism [174]

Therefore it has been suggested that a substance of exoge-nous or endogenous origin that is able to reverse any of theaforementioned mitochondrial deficits may facilitate a betterneuronal health and then be of interest of study as a potentialactive compound in AD therapy [175] In fact mitochondrialmedicine is emerging as a field of research focused on thefinding of therapeutic strategies to enhance mitochondrialfunction in aging and in those neurodegenerative diseasesin which it has been shown to be impaired [176ndash178] Thisavenue of investigation has led to the discovery of severalagents directly targeted to mitochondria that are able to delayor revert themitochondrial impairments associated toAD allavailable information on these compounds is reviewed belowand collected in Table 2 and schematized in Figure 3

32 Mitochondria-Targeted Protective Compounds in AD

321 Synthetic Compounds Several mitochondria-targetedantioxidants have been designed by conjugating the lipophilictriphenylphosphonium (TPP+) cation to an antioxidantmoiety such as coenzyme Q (CoQ) obtaining as a resultcompounds like MitoQ [219] Due to its chemical natureMitoQ takes advantage of the large MMP for reaching highconcentrations in mitochondria and unlike isolated CoQit is an effective antioxidant in the absence of functionalETC [220 221] McManus et al demonstrated that MitoQ iseffective in preventing loss of spatial memory and delayingthe early neuropathology in a triple transgenic mouse modelof AD they evaluated its effect on mitochondrial deficiencyand found that MitoQ avoided the MMP drop and reducedthe apoptosis in cortical neurons by a decrease in caspase-3 activity [171] Another study employed a Caenorhabditiselegansmodel overexpressing human A120573 end evidenced thatMitoQ exerted protective effects on lifespan and A120573-inducedparalysis and markedly ameliorated the depletion of mito-chondrial lipid cardiolipin and increased the mitochondrialETC function by protecting complexes IV and I however itwas not able to reduce the A120573-induced mitochondrial DNAoxidative damage [201]

Recently Szeto developed a series of small cell-perme-able antioxidant peptides (SS peptides) that are known toprotect mitochondria from oxidative damage [222] SS31 (H-D-Arg-Dmt-Lys-Phe-NH2) is one of them and presents asequence motif that allows it to target mitochondria In anA12057325ndash35-induced AD model of mice hippocampal neurons

SS31 restored axonal transport ofmitochondria and displayedpromising protection and maintenance of mitochondrialfunction proved by an increase in the number of healthy andintact mitochondria and a reduction in the levels of fissionproteins matrix protein andCypD [162] Similar results werefound by Calkins et al [211] Manczak et al also revealed


Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro

isolatedcorticalmito

chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60

9Tricyclodecan-9-yl-

xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro

A12057325ndash35-exp

osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in

ducedratepithelialcells

mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro

A12057325ndash35-indu

cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xcaspase-3andPar-4expressio

ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon

drialstructuralgenes

norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon

driallengthanddensity

uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative

Invitro120573-amyloid-indu

cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a

ndA12057325ndash35-in

ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]

20 Oxidative Medicine and Cellular LongevityTa

ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol

Invitro12057325ndash35-in

ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish

amyloidprecursorprotein

ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp

ermeabilitytransitionpo

reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid

23-bis-dimethylcarbamoyloxy-6-(4-ethyl-p

iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p

iperazin-1-yl)-1-(234-trihydroxy-phenyl)-bu

tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho

xy-phenylhydrazonePAO

phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno

nsteroidalanti-inflammatorydrugs


III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3

MitoQ Mdivi-1 ASS234 pramipexole edaravone melatonin peroxiredoxin-6 nicotinamide caffeine tournefolic acid B gypenoside XVII acteoside ergothioneine (R)-lipoic acid N-acetylcysteine neuregulin-1 puerarin resistin

Mitochondrialpermeability

transition pore (MPTP)

Mitochondrialrespiratory chain

DNA damage

Tournefolic acid B trolox

MitoQ Mdivi-1 edaravone melatonin gypenoside XVII thymoquinone acteosidecaffeine ergothioneine glutathioneN-acetylcysteine neuregulin-1 probucol resistin vitamin C trolox

Apoptosis

Mdivi-1 melatonin (R)-lipoic acid caffeine

probucol zeolite

MitoQ Mdivi-1 melatonin peroxiredoxin-3 nicotinamide caffeine green tea leaf extract gelsolinmethylene blue peroxiredoxin-3 probucol resistin

Mitochondrial aconitase inhibition

Depletion of mitochondrial lipid cardiolipin

MitoQ

MitoQ resveratrol dimebon cyclosporin A pramipexole SS31

Melatonin glutathione 17-120573-estradiol

uarr ROS

uarr ROS

uarr ROS

uarr Cyp D (cyclophilin D) expressionuarr mPTP opening

darr ATP productiondarr Respiratory rate

membrane potentialdarr Mitochondrial

uarr ratio BaxBcl-2 uarr cytochrome C release)

Ca2+


uarr Cytosolic Ca2+

(uarr caspase 39 activation

acteoside colostrinin GLP-1 (9-36)amide

Figure 3 Mechanisms of mitochondrial dysfunction and mitochondria-targeted drugs that have produced beneficial effect in AD models

positive effects on mitochondria for SS31 it was able to nor-malize the number ofmitochondria and reduce the abnormalexpression of peroxiredoxins and mitochondrial structuralgenes that was present in an A120573

25ndash35-induced mouse N2acells AD model [200] Moreover the mitochondrial divisioninhibitor 1 (mdivi-1) attenuated the degree of apoptosis in anA120573-induced model of AD in BV-2 and primary microglialcells then counteracting another pathological feature of ADsuch as neuroinflammation this effect is probably mediatedthrough its effects on mitochondria since Mdivi-1 reversedabnormalmitochondrial fissionMMP loss CytC release andcaspase-3 activation [223] Besides these actions in a cybridcell model it also maintained mitochondrial integrity andfunction via a reduction of mitochondrial ROS productionand increases in CytC oxidase and SOD activities and ATPlevels [174] Another chemically synthesized compound suchas complex ASS234 a novel multipotent molecule that com-bines indolyl propargylamine and benzylpiperidinemoietieshas shown protective activities in an A120573

1ndash42-induced SH-SY5Yneuroblastoma cellsmodel of ADASS234 inhibited themitochondrial-mediated apoptotic pathway by reducing thelevels of cleaved caspases 3 and 9 and the levels of proteolysedPARP [182] The pyrazolone edaravone reversed the AD-likein vitromitochondrial insults in the transfected N2aSweΔ9cell model in which edaravone treatment increased cellviability attenuating oxidative stress and CytC release andimproving MMP in addition it diminished apoptotic ratethrough a decrease in the BaxBcl-2 ratio and a suppressionof caspase-3 activation [173] Also both R(+) and S(minus)stereoisomers of pramipexole exerted restorative effects inanother A120573-induced model of AD they were able to inhibitmitochondrial-mediated apoptotic process by inhibiting cas-pases activations [209]

Finally a very recent work has revealed a mitochon-drial-targeted protective action for the well-known acetyl-cholinesterase inhibitor donepezil which is clinically usedfor treating AD Donepezil displayed ameliorative effects onbehavioral deficits in APPPS1 double transgenic mice andenhanced the resistance of their brain mitochondria to theinduction of mPTP by calcium ions such action may bemediated by its lowering effect on mitochondrial A120573 level inbrain of treated animals which was also later confirmed invitro in isolated mitochondria from rat brainsThus it avoidsthe A120573

1ndash42-induced functional decay inmitochondria in suchAD model [224]

322 Endogenous Compounds Several compounds withendogenous origin have revealed interesting actions onmito-chondrial deficiencies of AD For instance the hormonemelatonin has been largely studied Dragicevic et al showedthat a pretreatment with melatonin protected cognitive func-tion in an APPsw mice model of AD A plausible mechanismfor the observed effect viamitochondria was tested in isolatedmitochondria frommice proving that melatonin could com-pletely restore mitochondrial respiratory rate MMP ROSproduction and energymetabolism other in vitro assays sug-gested a possible implication of c-AMP-dependent phospho-diesterase (PDE) 4 or cGMP-dependent PDE5 in the effectsdisplayed bymelatonin [169]The same group of research pre-viously demonstrated similar actions of melatonin in brainmitochondria isolated from the double transgenic APPPS1mice model of AD and determined that melatonin receptorsignaling is required for its full effect [170] Furthermoremelatonin evidenced mitochondrial protective activity in invitro models Besides acting as an antioxidant activator ofmitochondrial aconitase one of the enzymes of the citric


acid cycle that is affected by the oxidative stress in AD [179]melatoninwas reported to act as a defensive agent againstA120573-induced cytotoxicity in BV2microglial cells it attenuated thecellular apoptosis by activating Bcl-2 antiapoptotic pathwaysthus involving higher Bcl-2 expression and reduced BaxmRNA level and caspase-3 activity [197]

The endogenous antioxidant glutathione also acts as amitochondrial aconitase activator [179] and avoids the A120573-induced mitochondrial membrane depolarization in humanHCN-1A cells [193] Two mitochondrial metabolites suchas the acetyl-L-carnitine and the R-120572-lipoic acid (LA) haveattracted attention in AD-related research Aliev et al con-firmed that old rats fed with both compounds presentedsignificantly reduced number of damaged mitochondria andincreased number of intact mitochondria in hippocampusthus preventing from mitochondrial decay associated withage and AD [180] The organosulfur compound LA wasable to decrease the mitochondrial-related oxidative stressin fibroblasts from AD patients at a concentration of1mM LA attenuated AD-type mitochondrial dysfunctiongenerated by the cytochrome oxidase assembly inhibitor N-methylprotoporphyrin [196]

The neuroprotective role of peroxiredoxins (Prdx) 3 y6 the key mitochondrial antioxidant defense enzymes indetoxifying ROS such as H

2O2 has been evaluated with

results suggesting their therapeuticprophylactic potential toslow and attenuate AD progression and related neuronaldeath Rat PC12 cells overexpressing functional Prdx 6 pre-sented diminished A120573

25ndash35-induced mitochondrial apoptoticpathway expressed by an inhibition of PARP inactivationcaspases 3 and 9 activations and Bcl-2 and Bax dysreg-ulation [206] Meanwhile Chen et al evidenced the roleof Prdx 3 in improving cognition by using two transgenicmice models of AD (APP and APPPrdx3 models) Prdx3 activity was correlated with reduced brain amyloid betalevel and production and maintenance of mitochondrialintegrity and function showing reducedmitochondrial DNAoxidation and enhanced activity of mitochondrial complexesI and IV [205] Nicotinamide as an endogenous inhibitorof poly-ADP-ribose polymerase-1 (PARP-1) is evidenced todisplay reduction of oxidative stress in an A120573

1ndash42-inducedrat model and it upregulated mitochondrial function anddownregulated mitochondrial apoptosis lessening Bax levelsand increasing Bcl-2 levels [204]

323 Natural Products Finally numerous natural productsdeserve to be mentioned for their mitochondrial-targetedantioxidant activities Alkaloid caffeine is proved to exertsimilar activities to melatonin [169] and in its crude formresulting from decaffeination of coffee it reduced memoryimpairment and A120573

1ndash42 levels in hippocampus of an ADmouse model the J20 mouse line crude caffeine maintainedmitochondrial function as revealed by increased ATP lev-els and lower ROS generation and inhibited the apoptosismediated bymitochondria (reduced caspase-3 activity) [184]Polyphenol resveratrol a proven antioxidant with interestin AD [225] when tested in an A120573-induced N2a mousecells model normalized the number of mitochondria and

decreased the abnormal expression of peroxiredoxins andmitochondrial structural genes it also preserved mitochon-drial function in vivo by inhibiting CypD expression [200]Polyphenolic compound tournefolic acid B (TAB) has beenisolated from Tournefortia sarmentosa Lam (Boraginaceae)and investigated by Chi et al on an in vitromodel of AD whodemonstrated its neuroprotective effect via mitochondrialcaspase 8-tBid-cytochrome c pathway Actually 50120583M TABrevoked the A120573 protein-induced caspases 8 and 9 activa-tion significantly reduced the elevation of calcium level inmitochondria and delayed the release of CytC reduction inapoptosis was evidenced by an attenuation in mitochondrialtBid elevation without affecting A120573-mediated decrease inmitochondrial Bcl-2120572 [214]

Gypenoside XVII (GP-17) is a novel phytoestrogen iso-lated from Gynostemma pentaphyllum or Panax notoginsengthat due to its structure was found to confer neuropro-tection against A120573

25ndash35-induced neurotoxicity in PC12 cellsvia estrogen receptor-dependent activation of PI3KAkt andNrf2AREHO-1 pathways and inactivation of PI3KAktpathway regardingmitochondrial failures pretreatmentwithGP-17 (10 120583M) for 12 h is demonstrated to restore normalMMP and reduced CytC release and the enhanced apoptosisby inhibiting caspase-3 activation and cleavage [194] Thephytoestrogen genistein also showed its potency to upregu-late the mitochondrial NaK-ATPase activity in human ADbrains which is proved to be disturbed in the early phaseof the disease by ameliorating the energy metabolism inthe initiation of AD pathology genistein is presented as aninteresting candidate drug [191]

Wang et al evaluated the potential activity of acteosidean antioxidant phenylethanoid glycoside first extracted fromVerbascum sinuatum and named ldquoverbascosiderdquo on A120573

25ndash35-induced SHSY5Y cell injury They concluded that a pretreat-ment with acteoside for 15 h was effective for inhibiting ROSproduction and mitochondrial dysfunction and apoptoticpathway this modulation involved decrease in BaxBcl-2ratio cytochrome c release and the cleavage of caspase-3[181] Thymoquinone is the bioactive and most abundantconstituent of the volatile oil of black seed and has beendescribed as a promising antioxidant in in vitro AD modelsin part for its restorative action onMMP impairments due toA120573 neurotoxicity [212 213]

Concerning plant extracts a green tea leaf extract rich inepicatechin and epigallocatechin gallate was able to reversedamaging effects of AlCl

3in a rat model suggesting it might

be beneficial in AD It reduced the aluminium neurotoxicityvia antioxidant and mitochondrial protective effects such asan augment in CytC oxidase activity [226]

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Authorsrsquo Contribution

Carlos Fernandez-Moriano and Elena Gonzalez-Burgos con-tributed equally to this work


Acknowledgment

Thisworkwas supported by a doctoral grant from the SpanishMinistry of Education Culture and Sports (FPU) awarded toCarlos Fernandez-Moriano (no FPU1203824)

References

[1] L C Schenkel and M Bakovic ldquoFormation and regulationof mitochondrial membranesrdquo International Journal of CellBiology vol 2014 Article ID 709828 13 pages 2014

[2] S E Horvath and G Daum ldquoLipids of mitochondriardquo Progressin Lipid Research vol 52 no 4 pp 590ndash614 2013

[3] R W Taylor and D M Turnbull ldquoMitochondrial DNA muta-tions in human diseaserdquo Nature Reviews Genetics vol 6 no 5pp 389ndash402 2005

[4] N V Dudkina R Kouril K Peters H-P Braun and E JBoekema ldquoStructure and function of mitochondrial supercom-plexesrdquoBiochimica et BiophysicaActa vol 1797 no 6-7 pp 664ndash670 2010

[5] D G Brdiczka D B Zorov and S-S Sheu ldquoMitochondrialcontact sites their role in energy metabolism and apoptosisrdquoBiochimica et Biophysica Acta vol 1762 no 2 pp 148ndash163 2006

[6] L J Martin ldquoBiology of mitochondria in neurodegenerativediseasesrdquo Progress in Molecular Biology and Translational Sci-ence vol 107 pp 355ndash415 2012

[7] M T Lin and M F Beal ldquoMitochondrial dysfunction andoxidative stress in neurodegenerative diseasesrdquoNature vol 443no 7113 pp 787ndash795 2006

[8] J M Beitz ldquoParkinsonrsquos disease a reviewrdquo Frontiers in Bio-science vol 6 pp 65ndash74 2014

[9] J M Shulman P L De Jager and M B Feany ldquoParkinsonrsquos dis-ease genetics and pathogenesisrdquo Annual Review of PathologyMechanisms of Disease vol 6 pp 193ndash222 2011

[10] J Parkinson ldquoAn essay on the shaking palsyrdquo The Journal ofneuropsychiatry and clinical neurosciences vol 14 no 2 pp 223ndash236 2002

[11] T Pringsheim N Jette A Frolkis and T D Steeves ldquoTheprevalence of Parkinsonrsquos disease a systematic review andmeta-analysisrdquo Movement Disorders vol 29 no 13 pp 1583ndash15902014

[12] A Wright Willis B A Evanoff M Lian S R Criswell andB A Racette ldquoGeographic and ethnic variation in Parkinsondisease a population-based study of us medicare beneficiariesrdquoNeuroepidemiology vol 34 no 3 pp 143ndash151 2010

[13] B C L Lai and J K C Tsui ldquoEpidemiology of Parkinsonrsquosdiseaserdquo British Columbia Medical Journal vol 43 no 3 pp133ndash137 2001

[14] B R Thanvi S K Munshi N Vijaykumar and T C N LoldquoNeuropsychiatric non-motor aspects of Parkinsonrsquos diseaserdquoPostgraduateMedical Journal vol 79 no 936 pp 561ndash565 2003

[15] S Gandhi and NWWood ldquoGenome-wide association studiesthe key to unlocking neurodegenerationrdquoNature Neurosciencevol 13 no 7 pp 789ndash794 2010

[16] K Kieburtz and K B Wunderle ldquoParkinsonrsquos disease evidencefor environmental risk factorsrdquoMovementDisorders vol 28 no1 pp 8ndash13 2013

[17] H Kim ldquoAlpha-synuclein expression in patients with Parkin-sonrsquos disease a clinicianrsquos perspectiverdquo Experimental Neurobiol-ogy vol 22 no 2 pp 77ndash83 2013

[18] S Veeriah B S Taylor S Meng et al ldquoSomatic mutations of theParkinsonrsquos disease-associated gene PARK2 in glioblastoma andother human malignanciesrdquo Nature Genetics vol 42 no 1 pp77ndash82 2010

[19] B Bjorkblom A Adilbayeva J Maple-Groslashdem et al ldquoParkin-son disease protein DJ-1 binds metals and protects againstmetal-induced cytotoxicityrdquo Journal of Biological Chemistry vol288 no 31 pp 22809ndash22820 2013

[20] V A Morais P Verstreken A Roethig et al ldquoParkinsonrsquosdisease mutations in PINK1 result in decreased Complex Iactivity and deficient synaptic functionrdquo EMBO MolecularMedicine vol 1 no 2 pp 99ndash111 2009

[21] N L Khan S Jain J M Lynch et al ldquoMutations in the geneLRRK2 encoding dardarin (PARK8) cause familial Parkinsonrsquosdisease clinical pathological olfactory and functional imagingand genetic datardquo Brain vol 128 no 12 pp 2786ndash2796 2005

[22] A Moretto and C Colosio ldquoThe role of pesticide exposure inthe genesis of Parkinsonrsquos disease epidemiological studies andexperimental datardquo Toxicology vol 307 pp 24ndash34 2013

[23] A G Fitzmaurice S L Rhodes M Cockburn B Ritz and J MBronstein ldquoAldehyde dehydrogenase variation enhances effectof pesticides associated with Parkinson diseaserdquoNeurology vol82 no 5 pp 419ndash426 2014

[24] KM Powers T Smith-Weller GM FranklinW T LongstrethJr P D Swanson and H Checkoway ldquoParkinsonrsquos disease risksassociated with dietary iron manganese and other nutrientintakesrdquo Neurology vol 60 no 11 pp 1761ndash1766 2003

[25] X Gao H Chen T T Fung et al ldquoProspective study of dietarypattern and risk of Parkinson diseaserdquoThe American Journal ofClinical Nutrition vol 86 no 5 pp 1486ndash1494 2007

[26] X Yang and Y Xu ldquoMutations in theATP13A2 gene and parkin-sonism a preliminary reviewrdquo BioMed Research Internationalvol 2014 Article ID 371256 9 pages 2014

[27] D R Williams A Hadeed A S Najim Al-Din A-L Wreikatand A J Lees ldquoKufor Rakeb disease autosomal recessivelevodopa-responsive Parkinsonism with pyramidal degenera-tion supranuclear gaze palsy and dementiardquoMovement Disor-ders vol 20 no 10 pp 1264ndash1271 2005

[28] A Ramirez A Heimbach J Grundemann et al ldquoHeredi-tary parkinsonism with dementia is caused by mutations inATP13A2 encoding a lysosomal type 5 P-type ATPaserdquo NatureGenetics vol 38 no 10 pp 1184ndash1191 2006

[29] X Wang T G Petrie Y Liu J Liu H Fujioka and X ZhuldquoParkinsonrsquos disease-associated DJ-1 mutations impair mito-chondrial dynamics and cause mitochondrial dysfunctionrdquoJournal of Neurochemistry vol 121 no 5 pp 830ndash839 2012

[30] MW Dodson andM Guo ldquoPink1 Parkin DJ-1 andmitochon-drial dysfunction in Parkinsonrsquos diseaserdquo Current Opinion inNeurobiology vol 17 no 3 pp 331ndash337 2007

[31] K E Morrison ldquoParkin mutations and early onset parkinson-ismrdquo Brain vol 126 no 6 pp 1250ndash1251 2003

[32] J-Y Lee Y Nagano J P Taylor K L Lim and T-PYao ldquoDisease-causing mutations in Parkin impair mitochon-drial ubiquitination aggregation and HDAC6-dependent mit-ophagyrdquoThe Journal of Cell Biology vol 189 no 4 pp 671ndash6792010

[33] S Song S Jang J Park et al ldquoCharacterization of PINK1(PTEN-induced putative kinase 1) mutations associated withParkinson disease in mammalian cells and drosophilardquo TheJournal of Biological Chemistry vol 288 no 8 pp 5660ndash56722013


[34] A Kazlauskaite and M M Muqit ldquoPINK1 and Parkinmdashmito-chondrial interplay between phosphorylation and ubiquityla-tion in Parkinsonrsquos diseaserdquo FEBS Journal vol 282 no 2 pp215ndash223 2015

[35] H A Lashuel B M Petre J Wall et al ldquo120572-synuclein especiallythe parkinsonrsquos disease-associated mutants forms pore-likeannular and tubular protofibrilsrdquo Journal of Molecular Biologyvol 322 no 5 pp 1089ndash1102 2002

[36] L Stefanis ldquo120572-Synuclein in Parkinsonrsquos diseaserdquo Cold SpringHarbor Perspectives inMedicine vol 2 no 2 Article ID a0093992012

[37] J Q Li L Tan and J T Yu ldquoThe role of the LRRK2 gene inParkinsonismrdquo Molecular Neurodegeneration vol 9 article 472014

[38] I F Mata W J Wedemeyer M J Farrer J P Taylor and KA Gallo ldquoLRRK2 in Parkinsonrsquos disease protein domains andfunctional insightsrdquo Trends in Neurosciences vol 29 no 5 pp286ndash293 2006

[39] C Henchcliffe and M F Beal ldquoMitochondrial biology andoxidative stress in Parkinson disease pathogenesisrdquo NatureClinical Practice Neurology vol 4 no 11 pp 600ndash609 2008

[40] S R Subramaniam and M-F Chesselet ldquoMitochondrial dys-function and oxidative stress in Parkinsonrsquos diseaserdquo Progress inNeurobiology vol 106-107 pp 17ndash32 2013

[41] D N Hauser and T G Hastings ldquoMitochondrial dysfunctionand oxidative stress in Parkinsonrsquos disease and monogenicparkinsonismrdquoNeurobiology of Disease vol 51 pp 35ndash42 2013

[42] D Ebrahimi-Fakhari L Wahlster and P J McLean ldquoProteindegradation pathways in Parkinsonrsquos disease curse or blessingrdquoActa Neuropathologica vol 124 no 2 pp 153ndash172 2012

[43] A Bir O Sen S Anand et al ldquo120572-synuclein-induced mito-chondrial dysfunction in isolated preparation and intact cellsimplications in the pathogenesis of Parkinsonrsquos diseaserdquo Journalof Neurochemistry vol 131 no 6 pp 868ndash877 2014

[44] J W Langston P Ballard J W Tetrud and I Irwin ldquoChronicparkinsonism in humans due to a product of meperidine-analog synthesisrdquo Science vol 219 no 4587 pp 979ndash980 1983

[45] A H V Schapira J M Cooper D Dexter J B Clark P Jennerand C D Marsden ldquoMitochondrial complex I deficiency inParkinsonrsquos diseaserdquo Journal of Neurochemistry vol 54 no 3pp 823ndash827 1990

[46] V Dias E Junn and M M Mouradian ldquoThe role of oxidativestress in Parkinsonrsquos diseaserdquo Journal of Parkinsonrsquos Disease vol3 no 4 pp 461ndash491 2013

[47] R H Haas F Nasirian K Nakano et al ldquoLow plateletmitochondrial complex I and complex IIIII activity in earlyuntreated Parkinsonrsquos diseaserdquo Annals of Neurology vol 37 no6 pp 714ndash722 1995

[48] M Rana I de Coo F Diaz H Smeets and C T Moraes ldquoAnoutminusofminusframe cytochrome b gene deletion from a patient withparkinsonism is associated with impaired complex III assemblyand an increase in free radical productionrdquoAnnals of Neurologyvol 48 no 5 pp 774ndash781 2000

[49] A C Rego and C R Oliveira ldquoMitochondrial dysfunction andreactive oxygen species in excitotoxicity and apoptosis impli-cations for the pathogenesis of neurodegenerative diseasesrdquoNeurochemical Research vol 28 no 10 pp 1563ndash1574 2003

[50] S L Budd L Tenneti T Lishnak and S A Lipton ldquoMitochon-drial and extramitochondrial apoptotic signaling pathways incerebrocortical neuronsrdquo Proceedings of the National Academyof Sciences of the United States of America vol 97 no 11 pp6161ndash6166 2000

[51] M R Gluck and G D Zeevalk ldquoInhibition of brain mitochon-drial respiration by dopamine and its metabolites implicationsfor Parkinsonrsquos disease and catecholamine-associated diseasesrdquoJournal of Neurochemistry vol 91 no 4 pp 788ndash795 2004

[52] F H Khan T Sen A K Maiti S Jana U Chatterjee andS Chakrabarti ldquoInhibition of rat brain mitochondrial electrontransport chain activity by dopamine oxidation products duringextended in vitro incubation implications for Parkinsonrsquos dis-easerdquo Biochimica et Biophysica Acta Molecular Basis of Diseasevol 1741 no 1-2 pp 65ndash74 2005

[53] S Jana M Sinha D Chanda et al ldquoMitochondrial dysfunctionmediated by quinone oxidation products of dopamine implica-tions in dopamine cytotoxicity and pathogenesis of Parkinsonrsquosdiseaserdquo Biochimica et Biophysica Acta vol 1812 no 6 pp 663ndash673 2011

[54] V S Van Laar A J Mishizen M Cascio and T G HastingsldquoProteomic identification of dopamine-conjugated proteinsfrom isolated rat brain mitochondria and SH-SY5Y cellsrdquoNeurobiology of Disease vol 34 no 3 pp 487ndash500 2009

[55] T G Hastings ldquoThe role of dopamine oxidation in mitochon-drial dysfunction implications for Parkinsonrsquos diseaserdquo Journalof Bioenergetics and Biomembranes vol 41 no 6 pp 469ndash4722009

[56] S B Berman and T G Hastings ldquoDopamine oxidation altersmitochondrial respiration and induces permeability transitionin brain mitochondria implications for Parkinsonrsquos diseaserdquoJournal of Neurochemistry vol 73 no 3 pp 1127ndash1137 1999

[57] Y Luo H Umegaki X Wang R Abe and G S RothldquoDopamine induces apoptosis through an oxidation-involvedSAPKJNK activation pathwayrdquoThe Journal of Biological Chem-istry vol 273 no 6 pp 3756ndash3764 1998

[58] H J Choi S Y Lee Y Cho H No S W Kim and OHwang ldquoTetrahydrobiopterin causes mitochondrial dysfunc-tion in dopaminergic cells implications for Parkinsonrsquos diseaserdquoNeurochemistry International vol 48 no 4 pp 255ndash262 2008

[59] T E Gunter L Buntinas G Sparagna R Eliseev andKGunterldquoMitochondrial calcium transport mechanisms and functionsrdquoCell Calcium vol 28 no 5-6 pp 285ndash296 2000

[60] N B Pivovarova and S B Andrews ldquoCalcium-dependentmito-chondrial function and dysfunction in neurons minireviewrdquoThe FEBS Journal vol 277 no 18 pp 3622ndash3636 2010

[61] J P Sheehan R H Swerdlow W D Parker S W Miller RE Davis and J B Tuttle ldquoAltered calcium homeostasis in cellstransformedbymitochondria from individualswith Parkinsonrsquosdiseaserdquo Journal of Neurochemistry vol 68 no 3 pp 1221ndash12331997

[62] J Park Y Kim and J Chung ldquoMitochondrial dysfunction andParkinsonrsquos disease genes insights from Drosophilardquo DiseaseModels amp Mechanisms vol 2 no 7-8 pp 336ndash340 2009

[63] W Mandemakers V A Morais and B de Strooper ldquoA cell bio-logical perspective on mitochondrial dysfunction in Parkinsondisease and other neurodegenerative diseasesrdquo Journal of CellScience vol 120 no 10 pp 1707ndash1716 2007

[64] P P Hien H Gortnizka and R Kraemer ldquoRotenonemdashpotentialand prospect for sustainable agriculturerdquo Omonrice vol 11 pp83ndash92 2003

[65] A BManning-Bog A LMcCormack J Li V N Uversky A LFink and D A Di Monte ldquoThe herbicide paraquat causes up-regulation and aggregation of120572-synuclein inmice paraquat and120572-synucleinrdquoThe Journal of Biological Chemistry vol 277 no 3pp 1641ndash1644 2002


[66] N Simola M Morelli and A R Carta ldquoThe 6-hydroxydo-pamine model of Parkinsonrsquos diseaserdquo Neurotoxicity Researchvol 11 no 3-4 pp 151ndash167 2007

[67] G Patki and Y-S Lau ldquoMelatonin protects against neurobehav-ioral and mitochondrial deficits in a chronic mouse model ofParkinsonrsquos diseaserdquo Pharmacology Biochemistry and Behaviorvol 99 no 4 pp 704ndash711 2011

[68] K S Saravanan K M Sindhu and K P MohanakumarldquoMelatonin protects against rotenone-induced oxidative stressin a hemiparkinsonian rat modelrdquo Journal of Pineal Researchvol 42 no 3 pp 247ndash253 2007

[69] S C Sousa and R F Castilho ldquoProtective effect of melatoninon rotenone plus Ca2+-induced mitochondrial oxidative stressand PC12 cell deathrdquo Antioxidants and Redox Signaling vol 7no 9-10 pp 1110ndash1116 2005

[70] F Dabbeni-Sala S di Santo D Franceschini S D Skaperand P Giusti ldquoMelatonin protects against 6-OHDA-inducedneurotoxicity in rats a role for mitochondrial complex I activ-ityrdquo Federation of American Societies for Experimental BiologyJournal vol 15 no 1 pp 164ndash170 2001

[71] E Absi A Ayala A Machado and J Parrado ldquoProtectiveeffect of melatonin against the 1-methyl-4-phenylpyridinium-induced inhibition of complex I of the mitochondrial respira-tory chainrdquo Journal of Pineal Research vol 29 no 1 pp 40ndash472000

[72] P Mao C K Meshul P Thuillier N R S Goldberg and P HReddy ldquoCART peptide is a potential endogenous antioxidantand preferentially localized in mitochondriardquo PLoS ONE vol 7no 1 Article ID e29343 2012

[73] M E Solesio T A Prime A Logan et al ldquoThe mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrialfission in the 6-OHDA cell model of Parkinsonrsquos diseaserdquoBiochimica et Biophysica ActamdashMolecular Basis of Disease vol1832 no 1 pp 174ndash182 2013

[74] H S Chun and W C Low ldquoUrsodeoxycholic acid suppressesmitochondria-dependent programmed cell death induced bysodium nitroprusside in SH-SY5Y cellsrdquo Toxicology vol 292no 2-3 pp 105ndash112 2012

[75] D-W Li G-R Li Y Lu et al ldquo120572-lipoic acid protects dopamin-ergic neurons against MPP+-induced apoptosis by attenuatingreactive oxygen species formationrdquo International Journal ofMolecular Medicine vol 32 no 1 pp 108ndash114 2013

[76] A A Abdin and N I Sarhan ldquoIntervention of mitochon-drial dysfunction-oxidative stress-dependent apoptosis as apossible neuroprotective mechanism of 120572-lipoic acid againstrotenone-induced parkinsonism and l-dopa toxicityrdquo Neuro-science Research vol 71 no 4 pp 387ndash395 2011

[77] H Zhang H Jia J Liu et al ldquoCombined R-alpha-lipoic acidand acetyl-L-carnitine exerts efficient preventative effects in acellular model of Parkinsonrsquos diseaserdquo Journal of Cellular andMolecular Medicine vol 14 no 1-2 pp 215ndash225 2010

[78] S Bharath B C Cochran M Hsu J Liu B N Ames andJ K Andersen ldquoPre-treatment with R-lipoic acid alleviatesthe effects of GSH depletion in PC12 cells implications forParkinsonrsquos disease therapyrdquo NeuroToxicology vol 23 no 4-5pp 479ndash486 2002

[79] X Wang E Perez R Liu L J Yan R T Mallet and S HYang ldquoPyruvate protects mitochondria from oxidative stress inhumanneuroblastoma SK-N-SHcellsrdquoBrain Research vol 1132no 1 pp 1ndash9 2007

[80] L-Z Wang W-C Sun and X-Z Zhu ldquoEthyl pyruvate protectsPC12 cells from dopamine-induced apoptosisrdquo European Jour-nal of Pharmacology vol 508 no 1ndash3 pp 57ndash68 2005

[81] C Lu J Zhang X Shi et al ldquoNeuroprotective effects of tetram-ethylpyrazine against dopaminergic neuron injury in a ratmodel of Parkinsonrsquos disease induced by MPTPrdquo InternationalJournal of Biological Sciences vol 10 no 4 pp 350ndash357 2014

[82] Y-H Wang H-T Yu X-P Pu and G-H Du ldquoBaicalein pre-vents 6-hydroxydopamine-induced mitochondrial dysfunctionin SH-SY5Y cells via inhibition of mitochondrial oxidation andup-regulation of DJ-1 protein expressionrdquoMolecules vol 18 no12 pp 14726ndash14738 2013

[83] X-X Li G-R He X Mu et al ldquoProtective effects of baicaleinagainst rotenone-induced neurotoxicity in PC12 cells and iso-lated rat brain mitochondriardquo European Journal of Pharmacol-ogy vol 674 no 2-3 pp 227ndash233 2012

[84] H J Lee Y H Noh D Y Lee et al ldquoBaicalein attenuates6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cellsrdquoEuropean Journal of Cell Biology vol 84 no 11 pp 897ndash9052005

[85] R Barros Silva N A G Santos N M Martins et al ldquoCaf-feic acid phenethyl ester protects against the dopaminergicneuronal loss induced by 6-hydroxydopamine in ratsrdquo Neuro-science vol 233 pp 86ndash94 2013

[86] C Noelker M Bacher P Gocke et al ldquoThe flavanoide caf-feic acid phenethyl ester blocks 6-hydroxydopamine-inducedneurotoxicityrdquo Neuroscience Letters vol 383 no 1-2 pp 39ndash432005

[87] R L Jayaraj N Elangovan K Manigandan S Singh and SShukla ldquoCNB-001 a novel curcumin derivative guards dopa-mine neurons in MPTP model of Parkinsonrsquos diseaserdquo BioMedResearch International vol 2014 Article ID 236182 11 pages2014

[88] R L Jayaraj K Tamilselvam T Manivasagam and N Elan-govan ldquoNeuroprotective effect of CNB-001 a novel pyrazolederivative of curcumin on biochemical and apoptotic markersagainst rotenone-induced SK-N-SH cellular model of parkin-sonrsquos diseaserdquo Journal of Molecular Neuroscience vol 51 no 3pp 863ndash870 2013

[89] Z Liu Y Yu X Li C A Ross and W W Smith ldquoCurcuminprotects against A53T alpha-synuclein-induced toxicity in aPC12 inducible cell model for Parkinsonismrdquo PharmacologicalResearch vol 63 no 5 pp 439ndash444 2011

[90] B Jagatha R B Mythri S Vali and M M S Bharath ldquoCur-cumin treatment alleviates the effects of glutathione depletionin vitro and in vivo therapeutic implications for Parkinsonrsquosdisease explained via in silico studiesrdquo Free Radical Biology andMedicine vol 44 no 5 pp 907ndash917 2008

[91] J-Z Huang Y-Z Chen M Su et al ldquoDl-3-n-Butylphthalideprevents oxidative damage and reducesmitochondrial dysfunc-tion in anMPP+-induced cellularmodel of Parkinsonrsquos diseaserdquoNeuroscience Letters vol 475 no 2 pp 89ndash94 2010

[92] R Kuang Y Sun W Yuan L Lei and X Zheng ldquoProtectiveeffects of echinacoside one of the phenylethanoid glycosidesonH2O2-induced cytotoxicity in PC12 cellsrdquoPlantaMedica vol

75 no 14 pp 1499ndash1504 2009[93] NXiong J XiongGKhare et al ldquoEdaravone guards dopamine

neurons in a rotenone model for Parkinsonrsquos diseaserdquo PLoSONE vol 6 no 6 Article ID e20677 11 pages 2011

[94] S R Subramaniam and E M Ellis ldquoNeuroprotective effects ofumbelliferone and esculetin in a mouse model of Parkinsonrsquos


diseaserdquo Journal of Neuroscience Research vol 91 no 3 pp 453ndash461 2013

[95] K H Kim K Song S H Yoon O Shehzad Y S Kim and JH Son ldquoRescue of PINK1 protein null-specific mitochondrialcomplex IV deficits by ginsenoside Re activation of nitric oxidesignalingrdquo The Journal of Biological Chemistry vol 287 no 53pp 44109ndash44120 2012

[96] R B Mythri G Harish S K Dubey K Misra and M MSrinivas Bharath ldquoGlutamoyl diester of the dietary polyphenolcurcumin offers improved protection against peroxynitrite-mediated nitrosative stress and damage of brain mitochondriain vitro implications for Parkinsonrsquos diseaserdquo Molecular andCellular Biochemistry vol 347 no 1-2 pp 135ndash143 2011

[97] Y Han J Kim J Cho C S Lee and D Kim ldquoComparison ofthe protective effect of indole 120573-carbolines and R-(-)-deprenylagainst nitrogen Species-induced cell death in experimentalculture model of parkinsonrsquos diseaserdquo Journal of Clinical Neu-rology vol 1 no 1 pp 81ndash91 2005

[98] K Tamilselvam N Braidy T Manivasagam et al ldquoNeuropro-tective effects of hesperidin a plant flavanone on rotenone-induced oxidative stress and apoptosis in a cellular model forParkinsonrsquos diseaserdquoOxidative Medicine and Cellular Longevityvol 2013 Article ID 102741 11 pages 2013

[99] L-L Tian Z Zhou Q Zhang et al ldquoProtective effect of (+minus)isoborneol against 6-OHDA-induced apoptosis in SH-SY5Ycellsrdquo Cellular Physiology and Biochemistry vol 20 no 6 pp1019ndash1032 2007

[100] G Filomeni I Graziani D de Zio et al ldquoNeuroprotectionof kaempferol by autophagy in models of rotenone-mediatedacute toxicity possible implications for Parkinsonrsquos diseaserdquoNeurobiology of Aging vol 33 no 4 pp 767ndash785 2012

[101] F Yi X He and D Wang ldquoLycopene protects against MPP+-induced cytotoxicity by maintaining mitochondrial function inSH-SY5Y cellsrdquoNeurochemical Research vol 38 no 8 pp 1747ndash1757 2013

[102] H Kaur S Chauhan and R Sandhir ldquoProtective effect oflycopene on oxidative stress and cognitive decline in rotenoneinducedmodel of Parkinsonrsquos diseaserdquoNeurochemical Researchvol 36 no 8 pp 1435ndash1443 2011

[103] M B Bagh A K Maiti S Jana K Banerjee A Roy and SChakrabarti ldquoQuinone and oxyradical scavenging propertiesof N-acetylcysteine prevent dopamine mediated inhibition ofNa+ K+-ATPase and mitochondrial electron transport chainactivity in rat brain Implications in the neuroprotective therapyof Parkinsonrsquos diseaserdquo Free Radical Research vol 42 no 6 pp574ndash581 2008

[104] W-B Liu J Zhou YQu et al ldquoNeuroprotective effect of ostholeon MPP+-induced cytotoxicity in PC12 cells via inhibition ofmitochondrial dysfunction and ROS productionrdquo Neurochem-istry International vol 57 no 3 pp 206ndash215 2010

[105] P Shrivastava K Vaibhav R Tabassum et al ldquoAnti-apoptoticand anti-inflammatory effect of Piperine on 6-OHDA inducedParkinsonrsquos rat modelrdquo Journal of Nutritional Biochemistry vol24 no 4 pp 680ndash687 2013

[106] X Cai H Jia Z Liu et al ldquoPolyhydroxylated fullerene deriva-tive C

60(OH)

24prevents mitochondrial dysfunction and oxida-

tive damage in an MPP+-induced cellular model of Parkinsonrsquosdiseaserdquo Journal of Neuroscience Research vol 86 no 16 pp3622ndash3634 2008

[107] S Guan B Jiang Y M Bao and L J An ldquoProtocatechuicacid suppresses MPP+-induced mitochondrial dysfunction and

apoptotic cell death in PC12 cellsrdquo Food and Chemical Toxicol-ogy vol 44 no 10 pp 1659ndash1666 2006

[108] S S Karuppagounder S K Madathil M Pandey R HaobamU Rajamma and K P Mohanakumar ldquoQuercetin up-regulatesmitochondrial complex-I activity to protect against pro-grammed cell death in rotenone model of Parkinsonrsquos diseasein ratsrdquo Neuroscience vol 236 pp 136ndash148 2013

[109] J Bournival M Plouffe J Renaud C Provencher and M-G Martinoli ldquoQuercetin and sesamin protect dopaminergiccells from MPP+-induced neuroinflammation in a microglial(N9)-neuronal (PC12) coculture systemrdquo Oxidative Medicineand Cellular Longevity vol 2012 Article ID 921941 11 pages2012

[110] J Jiang J Jiang Y Zuo and Z Gu ldquoRapamycin protects themitochondria against oxidative stress and apoptosis in a ratmodel of Parkinsonrsquos diseaserdquo International Journal ofMolecularMedicine vol 31 no 4 pp 825ndash832 2013

[111] A Ferretta A Gaballo P Tanzarella et al ldquoEffect of resveratrolon mitochondrial function Implications in parkin-associatedfamiliar Parkinsonrsquos diseaserdquo Biochimica et Biophysica ActaMolecular Basis of Disease vol 1842 no 7 pp 902ndash915 2014

[112] P Ren H Jiang R Li et al ldquoRosmarinic acid inhibits 6-OHDA-induced neurotoxicity by anti-oxidation in MES235cellsrdquo Journal ofMolecularNeuroscience vol 39 no 1-2 pp 220ndash225 2009

[113] X-J Wang and J-X Xu ldquoSalvianic acid A protects human neu-roblastoma SH-SY5Y cells against MPP+-induced cytotoxicityrdquoNeuroscience Research vol 51 no 2 pp 129ndash138 2005

[114] L-L Tian X-J Wang Y-N Sun et al ldquoSalvianolic acid Ban antioxidant from Salvia miltiorrhiza prevents 6-hydroxy-dopamine induced apoptosis in SH-SY5Y cellsrdquo InternationalJournal of Biochemistry amp Cell Biology vol 40 no 3 pp 409ndash422 2008

[115] D-H Lee C-S Kim andY J Lee ldquoAstaxanthin protects againstMPTPMPP+-induced mitochondrial dysfunction and ROSproduction in vivo and in vitrordquo Food and Chemical Toxicologyvol 49 no 1 pp 271ndash280 2011

[116] P Dewapriya SWAHimaya Y-X Li and S-K Kim ldquoTyrosolexerts a protective effect against dopaminergic neuronal celldeath in in vitromodel of Parkinsonrsquos diseaserdquo Food Chemistryvol 141 no 2 pp 1147ndash1157 2013

[117] X-L Lu X-L Yao Z Liu et al ldquoProtective effects of xyloketal Bagainst MPP+-induced neurotoxicity in Caenorhabditis elegansand PC12 cellsrdquo Brain Research vol 1332 pp 110ndash119 2010

[118] K E Strathearn G G Yousef M H Grace et al ldquoNeuroprotec-tive effects of anthocyanin- and proanthocyanidin-rich extractsin cellular models of Parkinsonrsquos diseaserdquo Brain Research vol1555 pp 60ndash77 2014

[119] M Geed D Garabadu A Ahmad and S KrishnamurthyldquoSilibinin pretreatment attenuates biochemical and behavioralchanges induced by intrastriatal MPP+ injection in ratsrdquo Phar-macology Biochemistry amp Behavior vol 117 pp 92ndash103 2014

[120] S Guo E Bezard and B Zhao ldquoProtective effect of green teapolyphenols on the SH-SY5Y cells against 6-OHDA inducedapoptosis through ROS-NO pathwayrdquo Free Radical Biology andMedicine vol 39 no 5 pp 682ndash695 2005

[121] C K Hwang and H S Chun ldquoIsoliquiritigenin isolated fromlicorice Glycyrrhiza uralensis prevents 6-hydroxydopamine-induced apoptosis in dopaminergic neuronsrdquo Bioscience Bio-technology and Biochemistry vol 76 no 3 pp 536ndash543 2012

[122] S Hu R Han SMak and YHan ldquoProtection against 1-methyl-4-phenylpyridinium ion (MPP+)-induced apoptosis by water


extract of ginseng (Panax ginseng CA Meyer) in SH-SY5Ycellsrdquo Journal of Ethnopharmacology vol 135 no 1 pp 34ndash422011

[123] H G Kim M S Ju D-H Kim et al ldquoProtective effects ofChunghyuldan against ROS-mediated neuronal cell death inmodels of parkinsonrsquos diseaserdquo Basic amp Clinical Pharmacologyamp Toxicology vol 107 no 6 pp 958ndash964 2010

[124] H Hampel D Prvulovic S Teipel et al ldquoThe future ofAlzheimerrsquos disease the next 10 yearsrdquo Progress in Neurobiologyvol 95 no 4 pp 718ndash728 2011

[125] D J Selkoe and P J Lansbury ldquoAlzheimers disease is the mostcommon neurodegenerative disorderrdquo in Basic NeurochemistryMolecular Cellular andMedical Aspects J G Siegel BW Agra-noff R W Albers et al Eds Lippincott-Raven PhiladelphiaPa USA 6th edition 1999

[126] AlzheimerrsquosAssociation ldquoAlzheimerrsquos disease facts andfiguresrdquoAlzheimerrsquos amp Dementia vol 9 no 2 2013

[127] C W Zhu and M Sano ldquoEconomic considerations in themanagement of Alzheimerrsquos diseaserdquo Clinical Interventions inAging vol 1 no 2 pp 143ndash154 2006

[128] R Brookmeyer E Johnson K Ziegler-Graham and H MArrighi ldquoForecasting the global burden of Alzheimerrsquos diseaserdquoAlzheimerrsquos amp Dementia vol 3 no 3 pp 186ndash191 2007

[129] D J Selkoe ldquoAlzheimerrsquos disease genes proteins and therapyrdquoPhysiological Reviews vol 81 no 2 pp 741ndash766 2001

[130] M P Mattson ldquoPathways towards and away from Alzheimerrsquosdiseaserdquo Nature vol 430 no 7000 pp 631ndash639 2004

[131] J P Blass and G E Gibson ldquoCorrelations of disability andbiologic alterations in Alzheimer brain and test of significanceby a therapeutic trial in humansrdquo Journal of Alzheimerrsquos Diseasevol 9 no 2 pp 207ndash218 2006

[132] A Serrano-Pozo M P Frosch E Masliah and B T HymanldquoNeuropathological alterations in Alzheimer diseaserdquo ColdSpring Harbor Perspectives in Medicine vol 1 no 1 Article IDa006189 2011

[133] S Jiang Y Li C Zhang et al ldquoM1 muscarinic acetylcholinereceptor in Alzheimerrsquos diseaserdquo Neuroscience Bulletin vol 30no 2 pp 295ndash307 2014

[134] R N Kalaria G E Maestre R Arizaga et al ldquoAlzheimerrsquos dis-ease and vascular dementia in developing countries prevalencemanagement and risk factorsrdquoThe Lancet Neurology vol 7 no9 pp 812ndash826 2008

[135] R E Tanzi ldquoA brief history of Alzheimerrsquos disease genediscoveryrdquo Journal of Alzheimerrsquos Disease vol 33 supplement1 pp S5ndashS13 2013

[136] Q Zhou D T Peng X R Yuan et al ldquoAPOE and APOC1gene polymorphisms are associated with cognitive impairmentprogression in Chinese patients with late-onset Alzheimerrsquosdiseaserdquo Neural Regeneration Research vol 9 no 6 pp 653ndash660 2014

[137] J C de la Torre ldquoIs Alzheimerrsquos disease a neurodegenerative ora vascular disorder Data dogma and dialecticsrdquo The LancetNeurology vol 3 no 3 pp 184ndash190 2004

[138] Y Feng and X Wang ldquoAntioxidant therapies for Alzheimerrsquosdiseaserdquo Oxidative Medicine and Cellular Longevity vol 2012Article ID 472932 17 pages 2012

[139] M H Yana X Wang and X Zhu ldquoMitochondrial defects andoxidative stress in Alzheimer disease and Parkinson diseaserdquoFree Radical Biology and Medicine vol 62 pp 90ndash101 2013

[140] XHuang C S AtwoodMAHartshorn et al ldquoTheA120573peptideof Alzheimerrsquos disease directly produces hydrogen peroxide

through metal ion reductionrdquo Biochemistry vol 38 no 24 pp7609ndash7616 1999

[141] G Perry A D Cash and M A Smith ldquoAlzheimer disease andoxidative stressrdquo Journal of Biomedicine and Biotechnology vol2 no 3 pp 120ndash123 2002

[142] A Huber G Stuchbury A Burkle J Burnell and G MunchldquoNeuroprotective therapies for Alzheimerrsquos diseaserdquo CurrentPharmaceutical Design vol 12 no 6 pp 705ndash717 2006

[143] D J Bonda H-P Lee H-G Lee et al ldquoNovel therapeuticsfor Alzheimerrsquos disease an updaterdquo Current Opinion in DrugDiscovery amp Development vol 13 no 2 pp 235ndash246 2010

[144] R H Swerdlow ldquoThe neurodegenerativemitochondriopathiesrdquoJournal of Alzheimerrsquos Disease vol 17 no 4 pp 737ndash751 2009

[145] A Maruszak and C Zekanowski ldquoMitochondrial dysfunctionand Alzheimerrsquos diseaserdquo Progress in Neuro-Psychopharma-cology and Biological Psychiatry vol 35 no 2 pp 320ndash330 2011

[146] T Vargas C Ugalde C Spuch et al ldquoA120573 accumulation inchoroid plexus is associated with mitochondrial-induced apop-tosisrdquo Neurobiology of Aging vol 31 no 9 pp 1569ndash1581 2010

[147] SHauptmann I Scherping S Drose et al ldquoMitochondrial dys-function an early event in Alzheimer pathology accumulateswith age in AD transgenic micerdquoNeurobiology of Aging vol 30no 10 pp 1574ndash1586 2009

[148] Y G Kaminsky L A Tikhonova and E A Kosenko ldquoCriticalanalysis of Alzheimers amyloid-beta toxicity to mitochondriardquoFrontiers in Bioscience vol 20 pp 173ndash197 2015

[149] S M Cardoso S Santos R H Swerdlow and C R OliveiraldquoFunctional mitochondria are required for amyloid beta-mediated neurotoxicityrdquo The FASEB Journal vol 15 no 8 pp1439ndash1441 2001

[150] C Pereira M S Santos and C Oliveira ldquoMitochondrialfunction impairment induced by amyloid 120573-peptide on PC12cellsrdquo NeuroReport vol 9 no 8 pp 1749ndash1755 1998

[151] L Canevari J B Clark and T E Bates ldquo120573-Amyloid fragment25-35 selectively decreases complex IV activity in isolatedmitochondriardquo FEBS Letters vol 457 no 1 pp 131ndash134 1999

[152] P H Reddy S McWeeney B S Park et al ldquoGene expressionprofiles of transcripts in amyloid precursor protein transgenicmice Up-regulation of mitochondrial metabolism and apop-totic genes is an early cellular change in Alzheimerrsquos diseaserdquoHuman Molecular Genetics vol 13 no 12 pp 1225ndash1240 2004

[153] P Picone D Nuzzo L Caruana V Scafidi and M Di CarloldquoMitochondrial dysfunction different routes to Alzheimerrsquosdisease therapyrdquoOxidativeMedicine and Cellular Longevity vol2014 Article ID 780179 11 pages 2014

[154] M Manczak T S Anekonda E Henson B S Park J Quinnand P H Reddy ldquoMitochondria are a direct site of A betaaccumulation in Alzheimerrsquos disease neurons implicationsfor free radical generation and oxidative damage in diseaseprogressionrdquoHumanMolecular Genetics vol 15 no 9 pp 1437ndash1449 2006

[155] L Devi B M Prabhu D F Galati N G Avadhani and HK Anandatheerthavarada ldquoAccumulation of amyloid precur-sor protein in the mitochondrial import channels of humanAlzheimerrsquos disease brain is associated with mitochondrialdysfunctionrdquo Journal of Neuroscience vol 26 no 35 pp 9057ndash9068 2006

[156] M-Y Cha S-H Han S M Son et al ldquoMitochondria-specificaccumulation of amyloid 120573 induces mitochondrial dysfunctionleading to apoptotic cell deathrdquo PLoS ONE vol 7 no 4 ArticleID e34929 2012


[157] W K Hong E H Han D G Kim J Y Ahn J S Park andB G Han ldquoAmyloid-120573-peptide reduces the expression levelof mitochondrial cytochrome oxidase subunitsrdquoNeurochemicalResearch vol 32 no 9 pp 1483ndash1488 2007

[158] E M Mutisya A C Bowling and M F Beal ldquoCorticalcytochrome oxidase activity is reduced in Alzheimerrsquos diseaserdquoJournal of Neurochemistry vol 63 no 6 pp 2179ndash2184 1994

[159] H Atamna and R Kumar ldquoProtective role of methylene bluein Alzheimerrsquos disease via mitochondria and cytochrome c oxi-daserdquo Journal of Alzheimerrsquos Disease vol 20 no 1 supplement2 pp S439ndashS452 2010

[160] G S Zubenko and P Sauer ldquoSOD-1 activity and plateletmembrane fluidity inAlzheimerrsquos diseaserdquoBiological Psychiatryvol 25 no 6 pp 671ndash678 1989

[161] P I Moreira M S Santos C Sena E Nunes R Seica andC R Oliveira ldquoCoQ10 therapy attenuates amyloid beta-peptidetoxicity in brain mitochondria isolated from aged diabetic ratsrdquoExperimental Neurology vol 196 no 1 pp 112ndash119 2005

[162] P H Reddy R Tripathi Q Troung et al ldquoAbnormal mito-chondrial dynamics and synaptic degeneration as early eventsin Alzheimerrsquos disease implications to mitochondria-targetedantioxidant therapeuticsrdquo Biochimica et Biophysica ActamdashMolecular Basis of Disease vol 1822 no 5 pp 639ndash649 2012

[163] X Wang B Su H-G Lee et al ldquoImpaired balance of mito-chondrial fission and fusion in Alzheimerrsquos diseaserdquo Journal ofNeuroscience vol 29 no 28 pp 9090ndash9103 2009

[164] J G Begley W Duan S Chan K Duff and M P MattsonldquoAltered calcium homeostasis and mitochondrial dysfunctionin cortical synaptic compartments of presenilin-1 mutant micerdquoJournal of Neurochemistry vol 72 no 3 pp 1030ndash1039 1999

[165] M Obulesu and M J Lakshmi ldquoApoptosis in Alzheimerrsquosdisease an understanding of the physiology pathology andtherapeutic avenuesrdquoNeurochemical Research vol 39 no 12 pp2301ndash2312 2014

[166] A Eckert U Keil C AMarques et al ldquoMitochondrial dysfunc-tion apoptotic cell death and Alzheimerrsquos diseaserdquo BiochemicalPharmacology vol 66 no 8 pp 1627ndash1634 2003

[167] J Gotz and L M Ittner ldquoAnimal models of Alzheimerrsquos diseaseand frontotemporal dementiardquo Nature Reviews Neurosciencevol 9 no 7 pp 532ndash544 2008

[168] Z Feng C Qin Y Chang and J-T Zhang ldquoEarly melatoninsupplementation alleviates oxidative stress in a transgenicmouse model of Alzheimerrsquos diseaserdquo Free Radical Biology andMedicine vol 40 no 1 pp 101ndash109 2006

[169] N Dragicevic V Delic C Cao et al ldquoCaffeine increases mito-chondrial function and blocks melatonin signaling to mito-chondria in Alzheimerrsquos mice and cellsrdquo Neuropharmacologyvol 63 no 8 pp 1368ndash1379 2012

[170] N Dragicevic N Copes G OrsquoNeal-Moffitt et al ldquoMelatonintreatment restores mitochondrial function in Alzheimerrsquos micea mitochondrial protective role of melatonin membrane recep-tor signalingrdquo Journal of Pineal Research vol 51 no 1 pp 75ndash862011

[171] M J McManus M P Murphy and J L Franklin ldquoThemitochondria-targeted antioxidant mitoq prevents loss of spa-tial memory retention and early neuropathology in a transgenicmouse model of Alzheimerrsquos diseaserdquo Journal of Neurosciencevol 31 no 44 pp 15703ndash15715 2011

[172] S Sanz-Blasco R A Valero I Rodrıguez-Crespo C Villalobosand L Nunez ldquoMitochondrial Ca2+ overload underlies A120573oligomers neurotoxicity providing an unexpected mechanism

of neuroprotection by NSAIDsrdquo PLoS ONE vol 3 no 7 ArticleID e2718 2008

[173] Y Yan K Gong T Ma et al ldquoProtective effect of edaravoneagainst Alzheimerrsquos disease-relevant insults in neuroblastomaN2a cellsrdquoNeuroscience Letters vol 531 no 2 pp 160ndash165 2012

[174] X Gan S Huang L Wu et al ldquoInhibition of ERK-DLP1signaling and mitochondrial division alleviates mitochondrialdysfunction in Alzheimerrsquos disease cybrid cellrdquo Biochimica etBiophysica ActamdashMolecular Basis of Disease vol 1842 no 2 pp220ndash231 2014

[175] J Liu and B N Ames ldquoReducing mitochondrial decay withmitochondrial nutrients to delay and treat cognitive dysfunc-tion Alzheimerrsquos disease and Parkinsonrsquos diseaserdquo NutritionalNeuroscience vol 8 no 2 pp 67ndash89 2005

[176] P H Reddy ldquoRole of mitochondria in neurodegenerativediseases mitochondria as a therapeutic target in Alzheimerrsquosdiseaserdquo CNS Spectrums vol 14 no 8 supplement 7 pp 6ndash132009

[177] H Du and S S Yan ldquoMitochondrial medicine for neurodegen-erative diseasesrdquo International Journal of Biochemistry and CellBiology vol 42 no 5 pp 560ndash572 2010

[178] P I Moreira X Zhu XWang et al ldquoMitochondria a therapeu-tic target in neurodegenerationrdquo Biochimica et Biophysica Actavol 1802 no 1 pp 212ndash220 2010

[179] M Raukas R Rebane R Mahlapuu et al ldquoMitochondrialoxidative stress index activity of redox-sensitive aconitase andeffects of endogenous anti- and pro-oxidants on its activity incontrol Alzheimerrsquos disease and Swedish Familial Alzheimerrsquosdisease brainrdquo Free Radical Research vol 46 no 12 pp 1490ndash1495 2012

[180] G Aliev J Liu J C Shenk et al ldquoNeuronal mitochondrialamelioration by feeding acetyl-L-carnitine and lipoic acid toaged ratsrdquo Journal of Cellular and Molecular Medicine vol 13no 2 pp 320ndash333 2009

[181] H Wang Y Xu J Yan et al ldquoActeoside protects humanneuroblastoma SH-SY5Y cells against 120573-amyloid-induced cellinjuryrdquo Brain Research vol 1283 pp 139ndash147 2009

[182] I Bolea A Gella L Monjas et al ldquoMultipotent permeabledrug ASS234 inhibits A120573 aggregation possesses antioxidantproperties and protects from A120573-induced apoptosis in vitrordquoCurrent Alzheimer Research vol 10 no 8 pp 797ndash808 2013

[183] A Bacsi M Woodberry M L Kruzel and I BoldoghldquoColostrinin delays the onset of proliferative senescence ofdiploid murine fibroblast cellsrdquoNeuropeptides vol 41 no 2 pp93ndash101 2007

[184] Y-F Chu W-H Chang R M Black et al ldquoCrude caffeinereduces memory impairment and amyloid 120573

1minus42levels in an

Alzheimerrsquos mouse modelrdquo Food Chemistry vol 135 no 3 pp2095ndash2102 2012

[185] H Du L Guo F Fang et al ldquoCyclophilin D deficiency attenu-ates mitochondrial and neuronal perturbation and ameliorateslearning and memory in Alzheimerrsquos diseaserdquoNature Medicinevol 14 no 10 pp 1097ndash1105 2008

[186] M A Ansari G Joshi Q Huang et al ldquoIn vivo administrationof D609 leads to protection of subsequently isolated gerbil brainmitochondria subjected to in vitro oxidative stress induced byamyloid beta-peptide and other oxidative stressors relevance toAlzheimerrsquos disease and other oxidative stress-related neurode-generative disordersrdquo Free Radical Biology andMedicine vol 41no 11 pp 1694ndash1703 2006

[187] B Sheng K Gong Y Niu et al ldquoInhibition of 120574-secretase activ-ity reduces A120573 production reduces oxidative stress increases


mitochondrial activity and leads to reduced vulnerability toapoptosis implications for the treatment of Alzheimerrsquos dis-easerdquo Free Radical Biology and Medicine vol 46 no 10 pp1362ndash1375 2009

[188] S O Bachurin E P Shevtsova E G Kireeva G F Oxenkrugand S O Sablin ldquoMitochondria as a target for neurotoxins andneuroprotective agentsrdquo Annals of the New York Academy ofSciences vol 993 pp 334ndash344 2003

[189] J-H Jang O I Aruoma L-S Jen H Y Chung and Y-J SurhldquoErgothioneine rescues PC12 cells from beta-amyloid-inducedapoptotic deathrdquo Free Radical Biology and Medicine vol 36 no3 pp 288ndash299 2004

[190] T Vargas D Antequera C Ugalde C Spuch and E CarroldquoGelsolin restores A beta-induced alterations in choroid plexusepitheliumrdquo Journal of Biomedicine and Biotechnology vol 2010Article ID 805405 7 pages 2010

[191] C Kairane R Mahlapuu K Ehrlich M Zilmer and USoomets ldquoThe effects of different antioxidants on the activity ofcerebrocortical MnSOD and NaK-ATPase from post mortemAlzheimerrsquos disease and age-matched normal brainsrdquo CurrentAlzheimer Research vol 11 no 1 pp 79ndash85 2014

[192] T Ma X Du J E Pick G Sui M Brownlee and E KlannldquoGlucagon-like peptide-1 cleavage product GLP-1(9-36) amiderescues synaptic plasticity and memory deficits in Alzheimerrsquosdisease model micerdquo Journal of Neuroscience vol 32 no 40 pp13701ndash13708 2012

[193] S Medina M Martınez and A Hernanz ldquoAntioxidants inhibitthe human cortical neuron apoptosis induced by hydrogenperoxide tumor necrosis factor alpha dopamine and beta-amyloid peptide 1ndash42rdquo Free Radical Research vol 36 no 11 pp1179ndash1184 2002

[194] X Meng M Wang G Sun et al ldquoAttenuation of A12057325ndash35-induced parallel autophagic and apoptotic cell death by gypeno-side XVII through the estrogen receptor-dependent activationof Nrf2ARE pathwaysrdquo Toxicology and Applied Pharmacologyvol 279 no 1 pp 63ndash75 2014

[195] H Kawada K Blessing T Kiyota T Woolman L Winchesterand P F Kador ldquoEffects of multifunctional antioxidants onmitochondrial dysfunction and amyloid-120573metal dyshomeosta-sisrdquo Journal of Alzheimerrsquos Disease vol 44 no 1 pp 297ndash3072015

[196] P I Moreira P L R Harris X Zhu et al ldquoLipoic acid and N-acetyl cysteine decrease mitochondrial-related oxidative stressin Alzheimer disease patient fibroblastsrdquo Journal of AlzheimerrsquosDisease vol 12 no 2 pp 195ndash206 2007

[197] M-H Jang S-B Jung M-H Lee et al ldquoMelatonin attenuatesamyloid beta25-35-induced apoptosis in mouse microglial BV2cellsrdquo Neuroscience Letters vol 380 no 1-2 pp 26ndash31 2005

[198] W Dong F Huang W Fan et al ldquoDifferential effects of mela-tonin on amyloid-beta peptide 25ndash35-induced mitochondrialdysfunction in hippocampal neurons at different stages ofculturerdquo Journal of Pineal Research vol 48 no 2 pp 117ndash1252010

[199] A Gharib and H Atamna ldquoMethylene blue induces mitochon-drial complex IV and improves cognitive function and gripstrength in old micerdquo in Neurodegeneration Theory Disordersand Treatments chapter 3 pp 63ndash86 Nova Science New YorkNY USA 2010

[200] M Manczak P Mao M J Calkins et al ldquoMitochondria-targeted antioxidants protect against amyloid-beta toxicity inAlzheimerrsquos disease neuronsrdquo Journal of Alzheimerrsquos Diseasevol 20 no 2 pp S609ndashS631 2010

[201] L F Ng J Gruber I K Cheah et al ldquoThe mitochondria-targeted antioxidant MitoQ extends lifespan and improveshealthspan of a transgenic Caenorhabditis elegans model ofAlzheimer diseaserdquo Free Radical Biology and Medicine vol 71pp 390ndash401 2014

[202] R A S Robinson G Joshi Q Huang et al ldquoProteomic analysisof brain proteins in APPPS-1 human double mutant knock-in mice with increasing amyloid 120573-peptide deposition insightsinto the effects of in vivo treatment with N-acetylcysteine asa potential therapeutic intervention in mild cognitive impair-ment and Alzheimerrsquos diseaserdquo Proteomics vol 11 no 21 pp4243ndash4256 2012

[203] J Ryu H-N Yu H Cho et al ldquoNeuregulin-1 exerts protectiveeffects against neurotoxicities induced by C-terminal fragmentsof APP via ErbB4 receptorrdquo Journal of Pharmacological Sciencesvol 119 no 1 pp 73ndash81 2012

[204] E Turunc Bayrakdar Y Uyanikgil L Kanit E Koylu and AYalcin ldquoNicotinamide treatment reduces the levels of oxidativestress apoptosis and PARP-1 activity in A120573(1-42)-induced ratmodel of Alzheimerrsquos diseaserdquo Free Radical Research vol 48 no2 pp 146ndash158 2014

[205] L Chen R Na and Q Ran ldquoEnhanced defense againstmitochondrial hydrogen peroxide attenuates age-associatedcognition declinerdquo Neurobiology of Aging vol 35 no 11 pp2552ndash2561 2014

[206] I K Kim K J Lee S Rhee S B Seo and J H Pak ldquoProtectiveeffects of peroxiredoxin 6 overexpression on amyloid120573-inducedapoptosis in PC12 cellsrdquo Free Radical Research vol 47 no 10 pp836ndash846 2013

[207] J Li G Wang J Liu et al ldquoPuerarin attenuates amyloid-beta-induced cognitive impairment through suppression ofapoptosis in rat hippocampus in vivordquo European Journal ofPharmacology vol 649 no 1ndash3 pp 195ndash201 2010

[208] H Zhang Y Liu M Lao Z Ma and X Yi ldquoPuerarin pro-tects Alzheimerrsquos disease neuronal cybrids from oxidant-stressinduced apoptosis by inhibiting pro-death signaling pathwaysrdquoExperimental Gerontology vol 46 no 1 pp 30ndash37 2011

[209] N A Abramova D S Cassarino S M Khan T W Painterand J P Bennett Jr ldquoInhibition by R(+) or S(-) pramipexole ofcaspase activation and cell death induced by methylpyridiniumion or beta amyloid peptide in SH-SY5Y neuroblastomardquoJournal of Neuroscience Research vol 67 no 4 pp 494ndash5002002

[210] J Liu N Chi H Chen et al ldquoResistin protection against endo-genous A120573 neuronal cytotoxicity frommitochondrial pathwayrdquoBrain Research vol 1523 pp 77ndash84 2013

[211] M J Calkins M Manczak P Mao U Shirendeb and P HReddy ldquoImpaired mitochondrial biogenesis defective axonaltransport of mitochondria abnormal mitochondrial dynamicsand synaptic degeneration in a mouse model of Alzheimerrsquosdiseaserdquo Human Molecular Genetics vol 20 no 23 pp 4515ndash4529 2011

[212] A Khan K Vaibhav H Javed et al ldquoAttenuation of A120573-inducedneurotoxicity by thymoquinone via inhibition ofmitochondrialdysfunction and oxidative stressrdquo Molecular and Cellular Bio-chemistry vol 369 no 1-2 pp 55ndash65 2012

[213] A H Alhebshi M Gotoh and I Suzuki ldquoThymoquinoneprotects cultured rat primary neurons against amyloid 120573-induced neurotoxicityrdquo Biochemical and Biophysical ResearchCommunications vol 433 no 4 pp 362ndash367 2013

[214] C-W Chi Y-L Lin Y-H Wang C-F Chen C-N Wangand Y-J Shiao ldquoTournefolic acid B attenuates amyloid 120573


protein-mediated toxicity by abrogating the calciumoverload inmitochondria and retarding the caspase 8-truncated Bid-cyto-chrome c pathway in rat cortical neuronsrdquo European Journal ofPharmacology vol 586 no 1ndash3 pp 35ndash43 2008

[215] S H Lee K R Kim S Y Ryu et al ldquoImpaired short-termplasticity in mossy fiber synapses caused by mitochondrialdysfunction of dentate granule cells is the earliest synapticdeficit in a mouse model of Alzheimerrsquos diseaserdquo The Journalof Neuroscience vol 32 no 17 pp 5953ndash5963 2012

[216] S-Y Kook K-M Lee Y Kim et al ldquoHigh-dose of vitamin Csupplementation reduces amyloid plaque burden and amelio-rates pathological changes in the brain of 5XFAD micerdquo CellDeath and Disease vol 5 no 2 Article ID e1083 2014

[217] M J Santos R A Quintanilla A Toro et al ldquoPeroxisomalproliferation protects from 120573-amyloid neurodegenerationrdquoTheJournal of Biological Chemistry vol 280 no 49 pp 41057ndash41068 2005

[218] M Montinaro D Uberti G MacCarinelli S A Bonini GFerrari-Toninelli and M Memo ldquoDietary zeolite supplemen-tation reduces oxidative damage and plaque generation in thebrain of an Alzheimerrsquos disease mousemodelrdquo Life Sciences vol92 no 17ndash19 pp 903ndash910 2013

[219] P I Moreira S M Cardoso C M Pereira M S Santosand C R Oliveira ldquoMitochondria as a therapeutic targetin Alzheimerrsquos disease and diabetesrdquo CNS and NeurologicalDisordersmdashDrug Targets vol 8 no 6 pp 492ndash511 2009

[220] R A J Smith G F Kelso A M James and M P MurphyldquoTargeting coenzyme Q derivatives to mitochondriardquo Methodsin Enzymology vol 382 pp 45ndash67 2004

[221] C Lu D Zhang M Whiteman and J S Armstrong ldquoIsantioxidant potential of the mitochondrial targeted ubiquinonederivative MitoQ conserved in cells lacking mtDNArdquo Antioxi-dants and Redox Signaling vol 10 no 3 pp 651ndash660 2008

[222] H H Szeto ldquoMitochondria-targeted peptide antioxidantsnovel neuroprotective agentsrdquo The AAPS Journal vol 8 no 3pp 521ndash531 2006

[223] N Xie C Wang Y Lian C Wu H Zhang and Q ZhangldquoInhibition of mitochondrial fission attenuates A120573-inducedmicroglia apoptosisrdquo Neuroscience vol 256 pp 36ndash42 2014

[224] C Y Ye Y Lei X C Tang and H Y Zhang ldquoDonepezil atten-uates A120573-associated mitochondrial dysfunction and reducesmitochondrial A120573 accumulation in vivo and in vitrordquo Neu-ropharmacology vol 95 pp 29ndash36 2015

[225] S D Rege T Geetha G D Griffin T L Broderick and JR Babu ldquoNeuroprotective effects of resveratrol in Alzheimerdisease pathologyrdquoFrontiers inAgingNeuroscience vol 6 article218 2014

[226] A Jelenkovic M D Jovanovic I Stevanovic et al ldquoInfluenceof the green tea leaf extract on neurotoxicity of aluminiumchloride in ratsrdquo Phytotherapy Research vol 28 no 1 pp 82ndash87 2014

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


Consistent evidence suggests that mitochondrial failureis associated with early events in the pathogenesis of ageing-related neurodegenerative disorders including Parkinsonrsquosdisease and Alzheimerrsquos disease Mitochondria-targeted pro-tective compounds that prevent or minimize mitochondrialdysfunction constitute potential therapeutic strategies in theprevention and treatment of these central nervous systemdiseases [6 7] This paper provides an overview of theinvolvement ofmitochondrial dysfunction in Parkinsonrsquos andAlzheimerrsquos diseases with particular attention to in vitro andin vivo studies on promising endogenous and exogenousmitochondria-targeted protective compounds

2 Parkinsonrsquos Disease and Mitochondria-Targeted Protective Compounds

21 Parkinsonrsquos Disease (PD) Parkinsonrsquos disease is a chronicprogressive disorder characterized pathologically by the lossof dopaminergic neurons located in the substantia nigrapars compacta and to a lesser extent in putamen caudateand globus pallidus and by the formation of intracellularprotein inclusions of mainly alpha-synuclein (named asLewy bodies) in the remaining neurons [8 9] The firstclinical description was published in 1817 by the EnglishphysicianDr Parkinson in his work ldquoAn Essay on the ShakingPalsyrdquo [10] Parkinsonrsquos disease is the second most commonneurodegenerative disorder after Alzheimerrsquos disease whichaffects more than 63 million people over usually the ageof 60 worldwide Regarding epidemiology this age-relatedcentral nervous system disease appears to be slightly morecommon in whites than blacks and Asian people in menthan inwomen and in some geographical regions (ie ChinaIndia and USA) [11ndash13] The most relevant clinical featuresinclude tremor bradykinesia rigidity and dystonia howeverin addition to these characteristicmotor signs and symptomsneuropsychiatric and other nonmotor manifestations suchas depression cognitive impairment anxiety and psychosishave been also described [8 9 14] Although the exactcausal factors of Parkinsonrsquos disease remain unknown severalresearch studies point to specific genetic mutations andenvironmental factors [15 16] It has been estimated thataround 5ndash10 in every 100 people suffering from Parkinsonrsquosdisease are associated with gene mutations Scientifics haveidentified at least 13 gene mutations among which one couldhighlight those in the genes SNCA (synuclein alpha non-A4 component of amyloid precursor) PARK2 (Parkinsonrsquosdisease autosomal recessive juvenile 2) PARK7 (Parkinsonrsquosdisease autosomal recessive early-onset 7) PINK1 (PTEN-induced putative kinase 1) and LRRK2 (leucine-rich repeatkinase 2) [15]The SNCA gene encodes for the protein alpha-synuclein which is a key component of Lewy bodies thePARK2 gene encodes for the E3 ubiquitin ligase parkinwhich is implied in mitochondrial maintenance the PARK7gene encodes for the antioxidant protein DJ-1 PINK 1gene encodes for a serinethreonine-protein kinase with aprotective mitochondrial role Alterations of SNCA PARK2PARK7 and PINK1 genes are involved in the early-onsetParkinsonrsquos disease (this is diagnosed before being 50 years

old) [17ndash20]The LRRK2 gene which encodes for the proteindardarin has been associated with the late-onset Parkinsonrsquosdisease [21] The rest around 95 of diagnosed Parkinsonrsquosdisease cases are sporadic in which environmental factorssuch as pesticides and dietary factors among others seemto play a crucial role Researchers have identified severalcommon pesticides that their exposure may increase the riskof developing Parkinsonrsquos disease among which rotenoneparaquat dithiocarbamates (ie maneb ziram) pyrethroids(ie deltamethrin) organochlorine (dieldrin) imidazoles(ie triflumizole benomyl) and 22-dicarboximides (iefolpet aptan) are included [22 23] Regarding dietary factorsboth dietary patterns orand dietary nutrients that may pro-tect or may increase against to suffer from Parkinsonrsquos diseasehave been reported As an example in a case control studyperformed during ten years for establishing the influence ofminerals vitamins and fats in the etiology of Parkinsonrsquos dis-ease an association between a high intake of a combinationof iron and manganese and the development of Parkinsonrsquosdiseasewas found [24] On the other hand a large prospectivestudy performed over fifteen years with 49 692 men and81 676 women revealed that the high intake of fruit vegeta-bles legumes whole grains nuts fish and poultry the lowintake of saturated fat and the moderate intake of alcohol areprotective dietary patterns against Parkinsonrsquos disease [25]

211 Mitochondrial Dysfunction in Familial PD As we havepreviously commented around 5ndash10 of Parkinsonrsquos dis-ease cases involve gene products Mutations in ATP13A2(PARK9) DJ-1 (PARK7) parkin (PARK2) and PTEN-induced putative kinase 1 (PINK1) (PARK6) are associatedwith autosomal recessive PD and mutations in 120572-synucleingene and leucine-rich repeat kinase 2 gene (LRRK2) areimplicated in autosomal dominant PD (see Figure 1) [16]

Mutations in the ATP13A2 gene (PARK9) encodingfor a lysosomal type 5P-type ATPase cause a hereditaryrare juvenile onset autosomal recessive Parkinsonism withdementia named as Kufor-Rakeb syndrome This particularParkinsonrsquos form characterized by supranuclear gaze palsydystonia pyramidal signs and cognitive impairment wasfirst evidenced in 2006 in members of a nonconsanguineousChilean family The neuronal damage associated with muta-tions in this gene is related to alterations inmitochondria andlysosomes functions and divalent cation regulation [26ndash28]

DJ-1 mutations on chromosome 1p36 cause autosomalrecessive early-onset PD and its pathological mechanismseems to be linked with mitochondrial fragmentation andmitochondrial structural damage and consequently defects inthe mitochondrial function of dopaminergic cells [29 30]

Mutations in the parkin gene product which is an ubiqui-tin ligase lead to an early-onset familial Parkinsonrsquos diseaseand its first description dates in the year 1998 Experimentalstudies have determined that the pathology of parkin isassociated with alterations in the mitochondrial recogni-tion transportation and ubiquitination and with mitophagyimpairment [31 32]

Mutations in themitochondrial serinethreonine-proteinkinase PINK1 result in alterations in the mitochondrial


III

IIIIV

V

Alpha-synuclein

PINK1

ATP production

PINK1

ROS

PINK1

Parkin


LRRK2

LRRK2


DJ-1

DJ-1

DJ-1

















III

IIIIV

V

Mitochondrial DNA

DNA damage

Apoptosis


Mitochondrial

Mitochondrial



respiratory chain






uarr ROS


darr ATP production

Ca2+


uarr Cytosolic Ca2+








diseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Acetyl-L-carnitin

eQuaternary

ammon

ium

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[65]

Astaxanthin

Non

provitamin

Acaroteno

id

MPP

(+)-indu

cedmou

semod

elIn

vitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

MPP

+-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcaspase-3

[81]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lmaintainmito

chon

drialredox

activ

ity[82]

Baicalein

Flavon

oid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

eland

isolatedratb

rain

mito

chon

driaof

roteno

neindu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrintracellularA

TPprod

uctio

n

[83]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lInhibitio

nof

them

itochon

drialapo

ptoticpathway


darrp-c-JunN-te

rminalkinase

(JNK)

[84]

Caffeicacid

phenethyleste

rPh

enoliccompo

und

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


n

[85]

Prim

arycultu

reso

fcerebellarg

ranu

leneuron

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

darrcytochromec

release

[86]

CNB-001

Pyrazolederiv

ativeo

fcurcum

in

MPT

P-indu

cedrodent

PDmod

elMaintenance

ofno

rmalmito

chon

drialm

orph

olog

yandsiz

e[87]

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

l

[88]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Curcum

inPo

lyph

enol

PC12

cells

mutantA


ducedcelldeath

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n

[89]

Mou

sebrainandthe1RB

3AN27

(N27)ratdo

paminergic

neuron

alcelllin

emod

elof

buthionine

sulfo

ximine-indu

cedPD

Maintenance

ofmito

chon


nuarractiv

ities

ofcomplex

Idarroxidatived

amagetoproteins

uarrglutathion

e

[90]

DL-3-n-

butylphthalid

e(N

BP)

Synthetic

compo

und

basedon

L-3-n-bu

tylphthalid

e

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[91]

Echinacosid

ePh

enylethano

idglycoside

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

H2O

2-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

[92]

Edaravon

ePy

razolederiv

ative

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xMaintenance

ofmito

chon


ndarrRO

Sgeneratio

n

[93]

Esculetin

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ginseno

sideR

ePanaxatriolsapon

inPINK1

nullcells

Reversingthed

eficitincomplex

IVactiv

ity

uarrLR

PPRC

Hsp90and

Hsp60

levels

[95]

Glutamoyld

ieste

rof

curcum

inPo

lyph

enol

Mou

sebrainmito

chon

driaindu

ced-peroxynitrite

PDMaintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[96]

Harmalol

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Harmine

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Hesperid

inPo

lyph

enol

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[98]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Isob

orneol

Mon

oterpeno

idalcoho

lIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[99]

Kaem

pferol

Flavon

oid

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

eland

prim

aryneuron

sofrotenon

e-indu

cedPD

uarrAu

toph

agy

[100]

120572-Lipoica

cid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[75]

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[76]

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[77]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

PD

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[78]

Lycopene

Caroteno

id

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrlip

idperoxidatio

nuarrintracellularA

TPprod

uctio

nuarrmito

chon

drialD

NAcopy

numbersandmito

chon

drialR

NA

transcrip

tlevels

[101]

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

Dactiv

ityuarrglutathion

e

[102]

MPT

P-indu

cedmiceP

Dmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

luarrantio

xidant

enzymelevels

uarrintracellularA

TPprod

uctio

n

[67]

Roteno

ne-in

ducedratP

Dmod

el

Maintenance

ofmito

chon


ndarrRO

Sgeneratio

nuarrglutathion

euarrSO

Dandcatalase

activ

ities

[68]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Melaton

inHormon

eRo

teno

ne-in

ducediso

latedratb

rain

mito

chon

driaPD

mod

elMaintenance

ofmito

chon


ndarrCa

2+levels

darrRO

Sgeneratio

n[69]

6-OHDA-

indu

cedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[70]

MPP

(+)-indu

cediso

latedratliver

mito

chon

driaandstr

iatal

synaptosom

esPD

mod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[71]

Mito

Q(m

itoqu

inon

emesylate)

mdashIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xdarrDrp1

[73]

N-Acetylcysteine

Aminoacid

deriv

ativeH

2O2andtoxicq

uino

nesd

erived

from

dopamine-indu

cedrat

PDmod

el

Maintenance

ofmito

chon


nuarrmito

chon

drialrespiratory

activ

ityuarrNa+

K+-AT

Pase

activ

ity[103]

Neuropeptidec

ocaine

andam

phetam

ine

regu

latedtranscrip

t(C

ART

)

Peptide

Invitro

human

neurob

lasto

maS

H-SY5

YHEK

293cellsand

cultu

reso

fcortic

alandhipp

ocam

paln

eurons

ofH

2O2-indu

ced

PD

Maintenance

ofmito

chon


nprotectio

nof

mito

chon

drialD

NA(m

tDNA)cellu

larp

roteins

andlip

ids

[78]

Osth

ole

Cou

marin

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[104]

Piperin

eAlkaloid

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

[105]

Polyhydroxylated

fullerene

deriv

ative

C(60)(OH)(24)

mdashIn

vitro

human

neurob

lasto

mac

ellsmod

elof

MPP

(+)-indu

ced

PD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarractiv

ities

ofcomplexes

Iand

IIdarroxidatived


[106]

Protocatechu

icacid

Polyph

enol

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrcaspase-3

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[107]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Pyruvate

Organicacid

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

H2O

2-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[79]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

dopamine-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrp53

darrnu

clear

translo

catio

nof

NF-kapp

aBInhibitio

nof

them

itochon

drialapo

ptoticpathway

[80]

Quercetin

Biofl

avon

oid

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


ndarrRO

Sgeneratio

nmaintainmito

chon

drialm

embranep

otentia

l[108]

Invitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[109]

Rapamycin

Macrolid

e6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

DandGSH

-PX

[110]

Resveratrol

Polyph

enol

Invitro

prim

aryfib

roblastscultu

resfrom

patie

ntsw

ithparkin

mutations

(PARK

2)

Maintenance

ofmito

chon


nuarrcomplex

Iactivity

uarrcitrates

ynthasea

ctivity


ption

uarrmito

chon

drialA

TPprod

uctio

ndarrlactatec

ontent

[111]

Rosm

arinicacid

Polyph

enol

Invitro

MES

235do

paminergicc

ellsmod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[112]

Salvianica

cidA

Polyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

x[113]

Salviano

licacid

BPo

lyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[114]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Sesamin

Lign

anIn

vitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[22]

Tetram

ethylpyrazine

Pyrazine

MPT

P-indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[115]

Tyrosol

Phenoliccompo

und

MPP

(+)-indu

cedCA

THacells

PDmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia


TPprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

(i)activ

ationof

PI3K

Akt

signalling

pathway

[116]

Umbelliferone

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ursod

eoxycholic

acid

Second

arybileacids

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

SNP-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[74]

XyloketalB

Triterpenoid

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

eland

Caenorhabditiseleg

anso

fMPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[117]
















1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















III

IIIIV

V

Alpha-synuclein

PINK1

ATP production

PINK1

ROS

PINK1

Parkin


LRRK2

LRRK2


DJ-1

DJ-1

DJ-1

















III

IIIIV

V

Mitochondrial DNA

DNA damage

Apoptosis


Mitochondrial

Mitochondrial



respiratory chain






uarr ROS


darr ATP production

Ca2+


uarr Cytosolic Ca2+








diseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Acetyl-L-carnitin

eQuaternary

ammon

ium

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[65]

Astaxanthin

Non

provitamin

Acaroteno

id

MPP

(+)-indu

cedmou

semod

elIn

vitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

MPP

+-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcaspase-3

[81]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lmaintainmito

chon

drialredox

activ

ity[82]

Baicalein

Flavon

oid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

eland

isolatedratb

rain

mito

chon

driaof

roteno

neindu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrintracellularA

TPprod

uctio

n

[83]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lInhibitio

nof

them

itochon

drialapo

ptoticpathway


darrp-c-JunN-te

rminalkinase

(JNK)

[84]

Caffeicacid

phenethyleste

rPh

enoliccompo

und

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


n

[85]

Prim

arycultu

reso

fcerebellarg

ranu

leneuron

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

darrcytochromec

release

[86]

CNB-001

Pyrazolederiv

ativeo

fcurcum

in

MPT

P-indu

cedrodent

PDmod

elMaintenance

ofno

rmalmito

chon

drialm

orph

olog

yandsiz

e[87]

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

l

[88]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Curcum

inPo

lyph

enol

PC12

cells

mutantA


ducedcelldeath

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n

[89]

Mou

sebrainandthe1RB

3AN27

(N27)ratdo

paminergic

neuron

alcelllin

emod

elof

buthionine

sulfo

ximine-indu

cedPD

Maintenance

ofmito

chon


nuarractiv

ities

ofcomplex

Idarroxidatived

amagetoproteins

uarrglutathion

e

[90]

DL-3-n-

butylphthalid

e(N

BP)

Synthetic

compo

und

basedon

L-3-n-bu

tylphthalid

e

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[91]

Echinacosid

ePh

enylethano

idglycoside

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

H2O

2-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

[92]

Edaravon

ePy

razolederiv

ative

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xMaintenance

ofmito

chon


ndarrRO

Sgeneratio

n

[93]

Esculetin

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ginseno

sideR

ePanaxatriolsapon

inPINK1

nullcells

Reversingthed

eficitincomplex

IVactiv

ity

uarrLR

PPRC

Hsp90and

Hsp60

levels

[95]

Glutamoyld

ieste

rof

curcum

inPo

lyph

enol

Mou

sebrainmito

chon

driaindu

ced-peroxynitrite

PDMaintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[96]

Harmalol

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Harmine

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Hesperid

inPo

lyph

enol

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[98]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Isob

orneol

Mon

oterpeno

idalcoho

lIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[99]

Kaem

pferol

Flavon

oid

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

eland

prim

aryneuron

sofrotenon

e-indu

cedPD

uarrAu

toph

agy

[100]

120572-Lipoica

cid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[75]

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[76]

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[77]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

PD

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[78]

Lycopene

Caroteno

id

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrlip

idperoxidatio

nuarrintracellularA

TPprod

uctio

nuarrmito

chon

drialD

NAcopy

numbersandmito

chon

drialR

NA

transcrip

tlevels

[101]

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

Dactiv

ityuarrglutathion

e

[102]

MPT

P-indu

cedmiceP

Dmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

luarrantio

xidant

enzymelevels

uarrintracellularA

TPprod

uctio

n

[67]

Roteno

ne-in

ducedratP

Dmod

el

Maintenance

ofmito

chon


ndarrRO

Sgeneratio

nuarrglutathion

euarrSO

Dandcatalase

activ

ities

[68]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Melaton

inHormon

eRo

teno

ne-in

ducediso

latedratb

rain

mito

chon

driaPD

mod

elMaintenance

ofmito

chon


ndarrCa

2+levels

darrRO

Sgeneratio

n[69]

6-OHDA-

indu

cedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[70]

MPP

(+)-indu

cediso

latedratliver

mito

chon

driaandstr

iatal

synaptosom

esPD

mod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[71]

Mito

Q(m

itoqu

inon

emesylate)

mdashIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xdarrDrp1

[73]

N-Acetylcysteine

Aminoacid

deriv

ativeH

2O2andtoxicq

uino

nesd

erived

from

dopamine-indu

cedrat

PDmod

el

Maintenance

ofmito

chon


nuarrmito

chon

drialrespiratory

activ

ityuarrNa+

K+-AT

Pase

activ

ity[103]

Neuropeptidec

ocaine

andam

phetam

ine

regu

latedtranscrip

t(C

ART

)

Peptide

Invitro

human

neurob

lasto

maS

H-SY5

YHEK

293cellsand

cultu

reso

fcortic

alandhipp

ocam

paln

eurons

ofH

2O2-indu

ced

PD

Maintenance

ofmito

chon


nprotectio

nof

mito

chon

drialD

NA(m

tDNA)cellu

larp

roteins

andlip

ids

[78]

Osth

ole

Cou

marin

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[104]

Piperin

eAlkaloid

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

[105]

Polyhydroxylated

fullerene

deriv

ative

C(60)(OH)(24)

mdashIn

vitro

human

neurob

lasto

mac

ellsmod

elof

MPP

(+)-indu

ced

PD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarractiv

ities

ofcomplexes

Iand

IIdarroxidatived


[106]

Protocatechu

icacid

Polyph

enol

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrcaspase-3

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[107]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Pyruvate

Organicacid

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

H2O

2-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[79]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

dopamine-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrp53

darrnu

clear

translo

catio

nof

NF-kapp

aBInhibitio

nof

them

itochon

drialapo

ptoticpathway

[80]

Quercetin

Biofl

avon

oid

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


ndarrRO

Sgeneratio

nmaintainmito

chon

drialm

embranep

otentia

l[108]

Invitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[109]

Rapamycin

Macrolid

e6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

DandGSH

-PX

[110]

Resveratrol

Polyph

enol

Invitro

prim

aryfib

roblastscultu

resfrom

patie

ntsw

ithparkin

mutations

(PARK

2)

Maintenance

ofmito

chon


nuarrcomplex

Iactivity

uarrcitrates

ynthasea

ctivity


ption

uarrmito

chon

drialA

TPprod

uctio

ndarrlactatec

ontent

[111]

Rosm

arinicacid

Polyph

enol

Invitro

MES

235do

paminergicc

ellsmod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[112]

Salvianica

cidA

Polyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

x[113]

Salviano

licacid

BPo

lyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[114]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Sesamin

Lign

anIn

vitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[22]

Tetram

ethylpyrazine

Pyrazine

MPT

P-indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[115]

Tyrosol

Phenoliccompo

und

MPP

(+)-indu

cedCA

THacells

PDmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia


TPprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

(i)activ

ationof

PI3K

Akt

signalling

pathway

[116]

Umbelliferone

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ursod

eoxycholic

acid

Second

arybileacids

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

SNP-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[74]

XyloketalB

Triterpenoid

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

eland

Caenorhabditiseleg

anso

fMPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[117]
















1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
























III

IIIIV

V

Mitochondrial DNA

DNA damage

Apoptosis


Mitochondrial

Mitochondrial



respiratory chain






uarr ROS


darr ATP production

Ca2+


uarr Cytosolic Ca2+








diseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Acetyl-L-carnitin

eQuaternary

ammon

ium

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[65]

Astaxanthin

Non

provitamin

Acaroteno

id

MPP

(+)-indu

cedmou

semod

elIn

vitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

MPP

+-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcaspase-3

[81]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lmaintainmito

chon

drialredox

activ

ity[82]

Baicalein

Flavon

oid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

eland

isolatedratb

rain

mito

chon

driaof

roteno

neindu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrintracellularA

TPprod

uctio

n

[83]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lInhibitio

nof

them

itochon

drialapo

ptoticpathway


darrp-c-JunN-te

rminalkinase

(JNK)

[84]

Caffeicacid

phenethyleste

rPh

enoliccompo

und

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


n

[85]

Prim

arycultu

reso

fcerebellarg

ranu

leneuron

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

darrcytochromec

release

[86]

CNB-001

Pyrazolederiv

ativeo

fcurcum

in

MPT

P-indu

cedrodent

PDmod

elMaintenance

ofno

rmalmito

chon

drialm

orph

olog

yandsiz

e[87]

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

l

[88]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Curcum

inPo

lyph

enol

PC12

cells

mutantA


ducedcelldeath

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n

[89]

Mou

sebrainandthe1RB

3AN27

(N27)ratdo

paminergic

neuron

alcelllin

emod

elof

buthionine

sulfo

ximine-indu

cedPD

Maintenance

ofmito

chon


nuarractiv

ities

ofcomplex

Idarroxidatived

amagetoproteins

uarrglutathion

e

[90]

DL-3-n-

butylphthalid

e(N

BP)

Synthetic

compo

und

basedon

L-3-n-bu

tylphthalid

e

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[91]

Echinacosid

ePh

enylethano

idglycoside

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

H2O

2-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

[92]

Edaravon

ePy

razolederiv

ative

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xMaintenance

ofmito

chon


ndarrRO

Sgeneratio

n

[93]

Esculetin

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ginseno

sideR

ePanaxatriolsapon

inPINK1

nullcells

Reversingthed

eficitincomplex

IVactiv

ity

uarrLR

PPRC

Hsp90and

Hsp60

levels

[95]

Glutamoyld

ieste

rof

curcum

inPo

lyph

enol

Mou

sebrainmito

chon

driaindu

ced-peroxynitrite

PDMaintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[96]

Harmalol

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Harmine

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Hesperid

inPo

lyph

enol

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[98]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Isob

orneol

Mon

oterpeno

idalcoho

lIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[99]

Kaem

pferol

Flavon

oid

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

eland

prim

aryneuron

sofrotenon

e-indu

cedPD

uarrAu

toph

agy

[100]

120572-Lipoica

cid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[75]

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[76]

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[77]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

PD

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[78]

Lycopene

Caroteno

id

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrlip

idperoxidatio

nuarrintracellularA

TPprod

uctio

nuarrmito

chon

drialD

NAcopy

numbersandmito

chon

drialR

NA

transcrip

tlevels

[101]

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

Dactiv

ityuarrglutathion

e

[102]

MPT

P-indu

cedmiceP

Dmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

luarrantio

xidant

enzymelevels

uarrintracellularA

TPprod

uctio

n

[67]

Roteno

ne-in

ducedratP

Dmod

el

Maintenance

ofmito

chon


ndarrRO

Sgeneratio

nuarrglutathion

euarrSO

Dandcatalase

activ

ities

[68]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Melaton

inHormon

eRo

teno

ne-in

ducediso

latedratb

rain

mito

chon

driaPD

mod

elMaintenance

ofmito

chon


ndarrCa

2+levels

darrRO

Sgeneratio

n[69]

6-OHDA-

indu

cedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[70]

MPP

(+)-indu

cediso

latedratliver

mito

chon

driaandstr

iatal

synaptosom

esPD

mod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[71]

Mito

Q(m

itoqu

inon

emesylate)

mdashIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xdarrDrp1

[73]

N-Acetylcysteine

Aminoacid

deriv

ativeH

2O2andtoxicq

uino

nesd

erived

from

dopamine-indu

cedrat

PDmod

el

Maintenance

ofmito

chon


nuarrmito

chon

drialrespiratory

activ

ityuarrNa+

K+-AT

Pase

activ

ity[103]

Neuropeptidec

ocaine

andam

phetam

ine

regu

latedtranscrip

t(C

ART

)

Peptide

Invitro

human

neurob

lasto

maS

H-SY5

YHEK

293cellsand

cultu

reso

fcortic

alandhipp

ocam

paln

eurons

ofH

2O2-indu

ced

PD

Maintenance

ofmito

chon


nprotectio

nof

mito

chon

drialD

NA(m

tDNA)cellu

larp

roteins

andlip

ids

[78]

Osth

ole

Cou

marin

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[104]

Piperin

eAlkaloid

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

[105]

Polyhydroxylated

fullerene

deriv

ative

C(60)(OH)(24)

mdashIn

vitro

human

neurob

lasto

mac

ellsmod

elof

MPP

(+)-indu

ced

PD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarractiv

ities

ofcomplexes

Iand

IIdarroxidatived


[106]

Protocatechu

icacid

Polyph

enol

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrcaspase-3

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[107]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Pyruvate

Organicacid

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

H2O

2-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[79]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

dopamine-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrp53

darrnu

clear

translo

catio

nof

NF-kapp

aBInhibitio

nof

them

itochon

drialapo

ptoticpathway

[80]

Quercetin

Biofl

avon

oid

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


ndarrRO

Sgeneratio

nmaintainmito

chon

drialm

embranep

otentia

l[108]

Invitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[109]

Rapamycin

Macrolid

e6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

DandGSH

-PX

[110]

Resveratrol

Polyph

enol

Invitro

prim

aryfib

roblastscultu

resfrom

patie

ntsw

ithparkin

mutations

(PARK

2)

Maintenance

ofmito

chon


nuarrcomplex

Iactivity

uarrcitrates

ynthasea

ctivity


ption

uarrmito

chon

drialA

TPprod

uctio

ndarrlactatec

ontent

[111]

Rosm

arinicacid

Polyph

enol

Invitro

MES

235do

paminergicc

ellsmod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[112]

Salvianica

cidA

Polyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

x[113]

Salviano

licacid

BPo

lyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[114]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Sesamin

Lign

anIn

vitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[22]

Tetram

ethylpyrazine

Pyrazine

MPT

P-indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[115]

Tyrosol

Phenoliccompo

und

MPP

(+)-indu

cedCA

THacells

PDmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia


TPprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

(i)activ

ationof

PI3K

Akt

signalling

pathway

[116]

Umbelliferone

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ursod

eoxycholic

acid

Second

arybileacids

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

SNP-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[74]

XyloketalB

Triterpenoid

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

eland

Caenorhabditiseleg

anso

fMPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[117]
















1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















III

IIIIV

V

Mitochondrial DNA

DNA damage

Apoptosis


Mitochondrial

Mitochondrial



respiratory chain






uarr ROS


darr ATP production

Ca2+


uarr Cytosolic Ca2+








diseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Acetyl-L-carnitin

eQuaternary

ammon

ium

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[65]

Astaxanthin

Non

provitamin

Acaroteno

id

MPP

(+)-indu

cedmou

semod

elIn

vitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

MPP

+-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcaspase-3

[81]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lmaintainmito

chon

drialredox

activ

ity[82]

Baicalein

Flavon

oid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

eland

isolatedratb

rain

mito

chon

driaof

roteno

neindu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrintracellularA

TPprod

uctio

n

[83]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lInhibitio

nof

them

itochon

drialapo

ptoticpathway


darrp-c-JunN-te

rminalkinase

(JNK)

[84]

Caffeicacid

phenethyleste

rPh

enoliccompo

und

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


n

[85]

Prim

arycultu

reso

fcerebellarg

ranu

leneuron

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

darrcytochromec

release

[86]

CNB-001

Pyrazolederiv

ativeo

fcurcum

in

MPT

P-indu

cedrodent

PDmod

elMaintenance

ofno

rmalmito

chon

drialm

orph

olog

yandsiz

e[87]

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

l

[88]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Curcum

inPo

lyph

enol

PC12

cells

mutantA


ducedcelldeath

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n

[89]

Mou

sebrainandthe1RB

3AN27

(N27)ratdo

paminergic

neuron

alcelllin

emod

elof

buthionine

sulfo

ximine-indu

cedPD

Maintenance

ofmito

chon


nuarractiv

ities

ofcomplex

Idarroxidatived

amagetoproteins

uarrglutathion

e

[90]

DL-3-n-

butylphthalid

e(N

BP)

Synthetic

compo

und

basedon

L-3-n-bu

tylphthalid

e

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[91]

Echinacosid

ePh

enylethano

idglycoside

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

H2O

2-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

[92]

Edaravon

ePy

razolederiv

ative

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xMaintenance

ofmito

chon


ndarrRO

Sgeneratio

n

[93]

Esculetin

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ginseno

sideR

ePanaxatriolsapon

inPINK1

nullcells

Reversingthed

eficitincomplex

IVactiv

ity

uarrLR

PPRC

Hsp90and

Hsp60

levels

[95]

Glutamoyld

ieste

rof

curcum

inPo

lyph

enol

Mou

sebrainmito

chon

driaindu

ced-peroxynitrite

PDMaintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[96]

Harmalol

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Harmine

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Hesperid

inPo

lyph

enol

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[98]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Isob

orneol

Mon

oterpeno

idalcoho

lIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[99]

Kaem

pferol

Flavon

oid

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

eland

prim

aryneuron

sofrotenon

e-indu

cedPD

uarrAu

toph

agy

[100]

120572-Lipoica

cid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[75]

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[76]

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[77]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

PD

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[78]

Lycopene

Caroteno

id

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrlip

idperoxidatio

nuarrintracellularA

TPprod

uctio

nuarrmito

chon

drialD

NAcopy

numbersandmito

chon

drialR

NA

transcrip

tlevels

[101]

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

Dactiv

ityuarrglutathion

e

[102]

MPT

P-indu

cedmiceP

Dmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

luarrantio

xidant

enzymelevels

uarrintracellularA

TPprod

uctio

n

[67]

Roteno

ne-in

ducedratP

Dmod

el

Maintenance

ofmito

chon


ndarrRO

Sgeneratio

nuarrglutathion

euarrSO

Dandcatalase

activ

ities

[68]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Melaton

inHormon

eRo

teno

ne-in

ducediso

latedratb

rain

mito

chon

driaPD

mod

elMaintenance

ofmito

chon


ndarrCa

2+levels

darrRO

Sgeneratio

n[69]

6-OHDA-

indu

cedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[70]

MPP

(+)-indu

cediso

latedratliver

mito

chon

driaandstr

iatal

synaptosom

esPD

mod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[71]

Mito

Q(m

itoqu

inon

emesylate)

mdashIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xdarrDrp1

[73]

N-Acetylcysteine

Aminoacid

deriv

ativeH

2O2andtoxicq

uino

nesd

erived

from

dopamine-indu

cedrat

PDmod

el

Maintenance

ofmito

chon


nuarrmito

chon

drialrespiratory

activ

ityuarrNa+

K+-AT

Pase

activ

ity[103]

Neuropeptidec

ocaine

andam

phetam

ine

regu

latedtranscrip

t(C

ART

)

Peptide

Invitro

human

neurob

lasto

maS

H-SY5

YHEK

293cellsand

cultu

reso

fcortic

alandhipp

ocam

paln

eurons

ofH

2O2-indu

ced

PD

Maintenance

ofmito

chon


nprotectio

nof

mito

chon

drialD

NA(m

tDNA)cellu

larp

roteins

andlip

ids

[78]

Osth

ole

Cou

marin

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[104]

Piperin

eAlkaloid

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

[105]

Polyhydroxylated

fullerene

deriv

ative

C(60)(OH)(24)

mdashIn

vitro

human

neurob

lasto

mac

ellsmod

elof

MPP

(+)-indu

ced

PD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarractiv

ities

ofcomplexes

Iand

IIdarroxidatived


[106]

Protocatechu

icacid

Polyph

enol

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrcaspase-3

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[107]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Pyruvate

Organicacid

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

H2O

2-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[79]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

dopamine-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrp53

darrnu

clear

translo

catio

nof

NF-kapp

aBInhibitio

nof

them

itochon

drialapo

ptoticpathway

[80]

Quercetin

Biofl

avon

oid

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


ndarrRO

Sgeneratio

nmaintainmito

chon

drialm

embranep

otentia

l[108]

Invitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[109]

Rapamycin

Macrolid

e6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

DandGSH

-PX

[110]

Resveratrol

Polyph

enol

Invitro

prim

aryfib

roblastscultu

resfrom

patie

ntsw

ithparkin

mutations

(PARK

2)

Maintenance

ofmito

chon


nuarrcomplex

Iactivity

uarrcitrates

ynthasea

ctivity


ption

uarrmito

chon

drialA

TPprod

uctio

ndarrlactatec

ontent

[111]

Rosm

arinicacid

Polyph

enol

Invitro

MES

235do

paminergicc

ellsmod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[112]

Salvianica

cidA

Polyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

x[113]

Salviano

licacid

BPo

lyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[114]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Sesamin

Lign

anIn

vitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[22]

Tetram

ethylpyrazine

Pyrazine

MPT

P-indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[115]

Tyrosol

Phenoliccompo

und

MPP

(+)-indu

cedCA

THacells

PDmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia


TPprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

(i)activ

ationof

PI3K

Akt

signalling

pathway

[116]

Umbelliferone

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ursod

eoxycholic

acid

Second

arybileacids

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

SNP-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[74]

XyloketalB

Triterpenoid

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

eland

Caenorhabditiseleg

anso

fMPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[117]
















1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















diseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Acetyl-L-carnitin

eQuaternary

ammon

ium

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[65]

Astaxanthin

Non

provitamin

Acaroteno

id

MPP

(+)-indu

cedmou

semod

elIn

vitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

MPP

+-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcaspase-3

[81]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lmaintainmito

chon

drialredox

activ

ity[82]

Baicalein

Flavon

oid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

eland

isolatedratb

rain

mito

chon

driaof

roteno

neindu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrintracellularA

TPprod

uctio

n

[83]

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

lInhibitio

nof

them

itochon

drialapo

ptoticpathway


darrp-c-JunN-te

rminalkinase

(JNK)

[84]

Caffeicacid

phenethyleste

rPh

enoliccompo

und

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


n

[85]

Prim

arycultu

reso

fcerebellarg

ranu

leneuron

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

darrcytochromec

release

[86]

CNB-001

Pyrazolederiv

ativeo

fcurcum

in

MPT

P-indu

cedrodent

PDmod

elMaintenance

ofno

rmalmito

chon

drialm

orph

olog

yandsiz

e[87]

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

l

[88]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Curcum

inPo

lyph

enol

PC12

cells

mutantA


ducedcelldeath

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n

[89]

Mou

sebrainandthe1RB

3AN27

(N27)ratdo

paminergic

neuron

alcelllin

emod

elof

buthionine

sulfo

ximine-indu

cedPD

Maintenance

ofmito

chon


nuarractiv

ities

ofcomplex

Idarroxidatived

amagetoproteins

uarrglutathion

e

[90]

DL-3-n-

butylphthalid

e(N

BP)

Synthetic

compo

und

basedon

L-3-n-bu

tylphthalid

e

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[91]

Echinacosid

ePh

enylethano

idglycoside

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

H2O

2-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

[92]

Edaravon

ePy

razolederiv

ative

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xMaintenance

ofmito

chon


ndarrRO

Sgeneratio

n

[93]

Esculetin

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ginseno

sideR

ePanaxatriolsapon

inPINK1

nullcells

Reversingthed

eficitincomplex

IVactiv

ity

uarrLR

PPRC

Hsp90and

Hsp60

levels

[95]

Glutamoyld

ieste

rof

curcum

inPo

lyph

enol

Mou

sebrainmito

chon

driaindu

ced-peroxynitrite

PDMaintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[96]

Harmalol

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Harmine

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Hesperid

inPo

lyph

enol

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[98]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Isob

orneol

Mon

oterpeno

idalcoho

lIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[99]

Kaem

pferol

Flavon

oid

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

eland

prim

aryneuron

sofrotenon

e-indu

cedPD

uarrAu

toph

agy

[100]

120572-Lipoica

cid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[75]

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[76]

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[77]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

PD

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[78]

Lycopene

Caroteno

id

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrlip

idperoxidatio

nuarrintracellularA

TPprod

uctio

nuarrmito

chon

drialD

NAcopy

numbersandmito

chon

drialR

NA

transcrip

tlevels

[101]

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

Dactiv

ityuarrglutathion

e

[102]

MPT

P-indu

cedmiceP

Dmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

luarrantio

xidant

enzymelevels

uarrintracellularA

TPprod

uctio

n

[67]

Roteno

ne-in

ducedratP

Dmod

el

Maintenance

ofmito

chon


ndarrRO

Sgeneratio

nuarrglutathion

euarrSO

Dandcatalase

activ

ities

[68]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Melaton

inHormon

eRo

teno

ne-in

ducediso

latedratb

rain

mito

chon

driaPD

mod

elMaintenance

ofmito

chon


ndarrCa

2+levels

darrRO

Sgeneratio

n[69]

6-OHDA-

indu

cedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[70]

MPP

(+)-indu

cediso

latedratliver

mito

chon

driaandstr

iatal

synaptosom

esPD

mod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[71]

Mito

Q(m

itoqu

inon

emesylate)

mdashIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xdarrDrp1

[73]

N-Acetylcysteine

Aminoacid

deriv

ativeH

2O2andtoxicq

uino

nesd

erived

from

dopamine-indu

cedrat

PDmod

el

Maintenance

ofmito

chon


nuarrmito

chon

drialrespiratory

activ

ityuarrNa+

K+-AT

Pase

activ

ity[103]

Neuropeptidec

ocaine

andam

phetam

ine

regu

latedtranscrip

t(C

ART

)

Peptide

Invitro

human

neurob

lasto

maS

H-SY5

YHEK

293cellsand

cultu

reso

fcortic

alandhipp

ocam

paln

eurons

ofH

2O2-indu

ced

PD

Maintenance

ofmito

chon


nprotectio

nof

mito

chon

drialD

NA(m

tDNA)cellu

larp

roteins

andlip

ids

[78]

Osth

ole

Cou

marin

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[104]

Piperin

eAlkaloid

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

[105]

Polyhydroxylated

fullerene

deriv

ative

C(60)(OH)(24)

mdashIn

vitro

human

neurob

lasto

mac

ellsmod

elof

MPP

(+)-indu

ced

PD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarractiv

ities

ofcomplexes

Iand

IIdarroxidatived


[106]

Protocatechu

icacid

Polyph

enol

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrcaspase-3

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[107]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Pyruvate

Organicacid

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

H2O

2-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[79]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

dopamine-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrp53

darrnu

clear

translo

catio

nof

NF-kapp

aBInhibitio

nof

them

itochon

drialapo

ptoticpathway

[80]

Quercetin

Biofl

avon

oid

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


ndarrRO

Sgeneratio

nmaintainmito

chon

drialm

embranep

otentia

l[108]

Invitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[109]

Rapamycin

Macrolid

e6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

DandGSH

-PX

[110]

Resveratrol

Polyph

enol

Invitro

prim

aryfib

roblastscultu

resfrom

patie

ntsw

ithparkin

mutations

(PARK

2)

Maintenance

ofmito

chon


nuarrcomplex

Iactivity

uarrcitrates

ynthasea

ctivity


ption

uarrmito

chon

drialA

TPprod

uctio

ndarrlactatec

ontent

[111]

Rosm

arinicacid

Polyph

enol

Invitro

MES

235do

paminergicc

ellsmod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[112]

Salvianica

cidA

Polyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

x[113]

Salviano

licacid

BPo

lyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[114]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Sesamin

Lign

anIn

vitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[22]

Tetram

ethylpyrazine

Pyrazine

MPT

P-indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[115]

Tyrosol

Phenoliccompo

und

MPP

(+)-indu

cedCA

THacells

PDmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia


TPprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

(i)activ

ationof

PI3K

Akt

signalling

pathway

[116]

Umbelliferone

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ursod

eoxycholic

acid

Second

arybileacids

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

SNP-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[74]

XyloketalB

Triterpenoid

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

eland

Caenorhabditiseleg

anso

fMPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[117]
















1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Curcum

inPo

lyph

enol

PC12

cells

mutantA


ducedcelldeath

Inhibitio

nof

them

itochon

drialapo

ptoticpathway


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n

[89]

Mou

sebrainandthe1RB

3AN27

(N27)ratdo

paminergic

neuron

alcelllin

emod

elof

buthionine

sulfo

ximine-indu

cedPD

Maintenance

ofmito

chon


nuarractiv

ities

ofcomplex

Idarroxidatived

amagetoproteins

uarrglutathion

e

[90]

DL-3-n-

butylphthalid

e(N

BP)

Synthetic

compo

und

basedon

L-3-n-bu

tylphthalid

e

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[91]

Echinacosid

ePh

enylethano

idglycoside

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

H2O

2-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

[92]

Edaravon

ePy

razolederiv

ative

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xMaintenance

ofmito

chon


ndarrRO

Sgeneratio

n

[93]

Esculetin

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ginseno

sideR

ePanaxatriolsapon

inPINK1

nullcells

Reversingthed

eficitincomplex

IVactiv

ity

uarrLR

PPRC

Hsp90and

Hsp60

levels

[95]

Glutamoyld

ieste

rof

curcum

inPo

lyph

enol

Mou

sebrainmito

chon

driaindu

ced-peroxynitrite

PDMaintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[96]

Harmalol

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Harmine

Beta-carbo

line

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

SNAP-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[97]

Hesperid

inPo

lyph

enol

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

roteno

ne-in

ducedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[98]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Isob

orneol

Mon

oterpeno

idalcoho

lIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[99]

Kaem

pferol

Flavon

oid

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

eland

prim

aryneuron

sofrotenon

e-indu

cedPD

uarrAu

toph

agy

[100]

120572-Lipoica

cid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[75]

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[76]

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[77]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

PD

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[78]

Lycopene

Caroteno

id

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrlip

idperoxidatio

nuarrintracellularA

TPprod

uctio

nuarrmito

chon

drialD

NAcopy

numbersandmito

chon

drialR

NA

transcrip

tlevels

[101]

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

Dactiv

ityuarrglutathion

e

[102]

MPT

P-indu

cedmiceP

Dmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

luarrantio

xidant

enzymelevels

uarrintracellularA

TPprod

uctio

n

[67]

Roteno

ne-in

ducedratP

Dmod

el

Maintenance

ofmito

chon


ndarrRO

Sgeneratio

nuarrglutathion

euarrSO

Dandcatalase

activ

ities

[68]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Melaton

inHormon

eRo

teno

ne-in

ducediso

latedratb

rain

mito

chon

driaPD

mod

elMaintenance

ofmito

chon


ndarrCa

2+levels

darrRO

Sgeneratio

n[69]

6-OHDA-

indu

cedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[70]

MPP

(+)-indu

cediso

latedratliver

mito

chon

driaandstr

iatal

synaptosom

esPD

mod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[71]

Mito

Q(m

itoqu

inon

emesylate)

mdashIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xdarrDrp1

[73]

N-Acetylcysteine

Aminoacid

deriv

ativeH

2O2andtoxicq

uino

nesd

erived

from

dopamine-indu

cedrat

PDmod

el

Maintenance

ofmito

chon


nuarrmito

chon

drialrespiratory

activ

ityuarrNa+

K+-AT

Pase

activ

ity[103]

Neuropeptidec

ocaine

andam

phetam

ine

regu

latedtranscrip

t(C

ART

)

Peptide

Invitro

human

neurob

lasto

maS

H-SY5

YHEK

293cellsand

cultu

reso

fcortic

alandhipp

ocam

paln

eurons

ofH

2O2-indu

ced

PD

Maintenance

ofmito

chon


nprotectio

nof

mito

chon

drialD

NA(m

tDNA)cellu

larp

roteins

andlip

ids

[78]

Osth

ole

Cou

marin

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[104]

Piperin

eAlkaloid

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

[105]

Polyhydroxylated

fullerene

deriv

ative

C(60)(OH)(24)

mdashIn

vitro

human

neurob

lasto

mac

ellsmod

elof

MPP

(+)-indu

ced

PD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarractiv

ities

ofcomplexes

Iand

IIdarroxidatived


[106]

Protocatechu

icacid

Polyph

enol

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrcaspase-3

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[107]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Pyruvate

Organicacid

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

H2O

2-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[79]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

dopamine-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrp53

darrnu

clear

translo

catio

nof

NF-kapp

aBInhibitio

nof

them

itochon

drialapo

ptoticpathway

[80]

Quercetin

Biofl

avon

oid

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


ndarrRO

Sgeneratio

nmaintainmito

chon

drialm

embranep

otentia

l[108]

Invitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[109]

Rapamycin

Macrolid

e6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

DandGSH

-PX

[110]

Resveratrol

Polyph

enol

Invitro

prim

aryfib

roblastscultu

resfrom

patie

ntsw

ithparkin

mutations

(PARK

2)

Maintenance

ofmito

chon


nuarrcomplex

Iactivity

uarrcitrates

ynthasea

ctivity


ption

uarrmito

chon

drialA

TPprod

uctio

ndarrlactatec

ontent

[111]

Rosm

arinicacid

Polyph

enol

Invitro

MES

235do

paminergicc

ellsmod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[112]

Salvianica

cidA

Polyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

x[113]

Salviano

licacid

BPo

lyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[114]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Sesamin

Lign

anIn

vitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[22]

Tetram

ethylpyrazine

Pyrazine

MPT

P-indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[115]

Tyrosol

Phenoliccompo

und

MPP

(+)-indu

cedCA

THacells

PDmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia


TPprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

(i)activ

ationof

PI3K

Akt

signalling

pathway

[116]

Umbelliferone

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ursod

eoxycholic

acid

Second

arybileacids

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

SNP-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[74]

XyloketalB

Triterpenoid

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

eland

Caenorhabditiseleg

anso

fMPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[117]
















1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Isob

orneol

Mon

oterpeno

idalcoho

lIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[99]

Kaem

pferol

Flavon

oid

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

eland

prim

aryneuron

sofrotenon

e-indu

cedPD

uarrAu

toph

agy

[100]

120572-Lipoica

cid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invitro

ratadrenalph

eochromocytom

aPC1

2cells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[75]

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[76]

Invitro

human

neurob

lasto

maS

K-N-M

Ccells

mod

elof

roteno

ne-in

ducedPD

Maintenance

ofmito

chon


nuarrmito

chon

drialbiogenesis

darrRO

Sgeneratio

n[77]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

PD

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

uarrglutathion

e[78]

Lycopene

Caroteno

id

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrlip

idperoxidatio

nuarrintracellularA

TPprod

uctio

nuarrmito

chon

drialD

NAcopy

numbersandmito

chon

drialR

NA

transcrip

tlevels

[101]

Roteno

ne-in

ducedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

Dactiv

ityuarrglutathion

e

[102]

MPT

P-indu

cedmiceP

Dmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

luarrantio

xidant

enzymelevels

uarrintracellularA

TPprod

uctio

n

[67]

Roteno

ne-in

ducedratP

Dmod

el

Maintenance

ofmito

chon


ndarrRO

Sgeneratio

nuarrglutathion

euarrSO

Dandcatalase

activ

ities

[68]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Melaton

inHormon

eRo

teno

ne-in

ducediso

latedratb

rain

mito

chon

driaPD

mod

elMaintenance

ofmito

chon


ndarrCa

2+levels

darrRO

Sgeneratio

n[69]

6-OHDA-

indu

cedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[70]

MPP

(+)-indu

cediso

latedratliver

mito

chon

driaandstr

iatal

synaptosom

esPD

mod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[71]

Mito

Q(m

itoqu

inon

emesylate)

mdashIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xdarrDrp1

[73]

N-Acetylcysteine

Aminoacid

deriv

ativeH

2O2andtoxicq

uino

nesd

erived

from

dopamine-indu

cedrat

PDmod

el

Maintenance

ofmito

chon


nuarrmito

chon

drialrespiratory

activ

ityuarrNa+

K+-AT

Pase

activ

ity[103]

Neuropeptidec

ocaine

andam

phetam

ine

regu

latedtranscrip

t(C

ART

)

Peptide

Invitro

human

neurob

lasto

maS

H-SY5

YHEK

293cellsand

cultu

reso

fcortic

alandhipp

ocam

paln

eurons

ofH

2O2-indu

ced

PD

Maintenance

ofmito

chon


nprotectio

nof

mito

chon

drialD

NA(m

tDNA)cellu

larp

roteins

andlip

ids

[78]

Osth

ole

Cou

marin

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[104]

Piperin

eAlkaloid

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

[105]

Polyhydroxylated

fullerene

deriv

ative

C(60)(OH)(24)

mdashIn

vitro

human

neurob

lasto

mac

ellsmod

elof

MPP

(+)-indu

ced

PD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarractiv

ities

ofcomplexes

Iand

IIdarroxidatived


[106]

Protocatechu

icacid

Polyph

enol

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrcaspase-3

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[107]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Pyruvate

Organicacid

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

H2O

2-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[79]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

dopamine-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrp53

darrnu

clear

translo

catio

nof

NF-kapp

aBInhibitio

nof

them

itochon

drialapo

ptoticpathway

[80]

Quercetin

Biofl

avon

oid

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


ndarrRO

Sgeneratio

nmaintainmito

chon

drialm

embranep

otentia

l[108]

Invitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[109]

Rapamycin

Macrolid

e6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

DandGSH

-PX

[110]

Resveratrol

Polyph

enol

Invitro

prim

aryfib

roblastscultu

resfrom

patie

ntsw

ithparkin

mutations

(PARK

2)

Maintenance

ofmito

chon


nuarrcomplex

Iactivity

uarrcitrates

ynthasea

ctivity


ption

uarrmito

chon

drialA

TPprod

uctio

ndarrlactatec

ontent

[111]

Rosm

arinicacid

Polyph

enol

Invitro

MES

235do

paminergicc

ellsmod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[112]

Salvianica

cidA

Polyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

x[113]

Salviano

licacid

BPo

lyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[114]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Sesamin

Lign

anIn

vitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[22]

Tetram

ethylpyrazine

Pyrazine

MPT

P-indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[115]

Tyrosol

Phenoliccompo

und

MPP

(+)-indu

cedCA

THacells

PDmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia


TPprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

(i)activ

ationof

PI3K

Akt

signalling

pathway

[116]

Umbelliferone

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ursod

eoxycholic

acid

Second

arybileacids

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

SNP-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[74]

XyloketalB

Triterpenoid

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

eland

Caenorhabditiseleg

anso

fMPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[117]
















1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Melaton

inHormon

eRo

teno

ne-in

ducediso

latedratb

rain

mito

chon

driaPD

mod

elMaintenance

ofmito

chon


ndarrCa

2+levels

darrRO

Sgeneratio

n[69]

6-OHDA-

indu

cedratP

Dmod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[70]

MPP

(+)-indu

cediso

latedratliver

mito

chon

driaandstr

iatal

synaptosom

esPD

mod

elMaintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

Iactivity

[71]

Mito

Q(m

itoqu

inon

emesylate)

mdashIn

vitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xdarrDrp1

[73]

N-Acetylcysteine

Aminoacid

deriv

ativeH

2O2andtoxicq

uino

nesd

erived

from

dopamine-indu

cedrat

PDmod

el

Maintenance

ofmito

chon


nuarrmito

chon

drialrespiratory

activ

ityuarrNa+

K+-AT

Pase

activ

ity[103]

Neuropeptidec

ocaine

andam

phetam

ine

regu

latedtranscrip

t(C

ART

)

Peptide

Invitro

human

neurob

lasto

maS

H-SY5

YHEK

293cellsand

cultu

reso

fcortic

alandhipp

ocam

paln

eurons

ofH

2O2-indu

ced

PD

Maintenance

ofmito

chon


nprotectio

nof

mito

chon

drialD

NA(m

tDNA)cellu

larp

roteins

andlip

ids

[78]

Osth

ole

Cou

marin

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[104]

Piperin

eAlkaloid

6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

[105]

Polyhydroxylated

fullerene

deriv

ative

C(60)(OH)(24)

mdashIn

vitro

human

neurob

lasto

mac

ellsmod

elof

MPP

(+)-indu

ced

PD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarractiv

ities

ofcomplexes

Iand

IIdarroxidatived


[106]

Protocatechu

icacid

Polyph

enol

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrcaspase-3

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[107]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Pyruvate

Organicacid

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

H2O

2-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[79]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

dopamine-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrp53

darrnu

clear

translo

catio

nof

NF-kapp

aBInhibitio

nof

them

itochon

drialapo

ptoticpathway

[80]

Quercetin

Biofl

avon

oid

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


ndarrRO

Sgeneratio

nmaintainmito

chon

drialm

embranep

otentia

l[108]

Invitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[109]

Rapamycin

Macrolid

e6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

DandGSH

-PX

[110]

Resveratrol

Polyph

enol

Invitro

prim

aryfib

roblastscultu

resfrom

patie

ntsw

ithparkin

mutations

(PARK

2)

Maintenance

ofmito

chon


nuarrcomplex

Iactivity

uarrcitrates

ynthasea

ctivity


ption

uarrmito

chon

drialA

TPprod

uctio

ndarrlactatec

ontent

[111]

Rosm

arinicacid

Polyph

enol

Invitro

MES

235do

paminergicc

ellsmod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[112]

Salvianica

cidA

Polyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

x[113]

Salviano

licacid

BPo

lyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[114]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Sesamin

Lign

anIn

vitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[22]

Tetram

ethylpyrazine

Pyrazine

MPT

P-indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[115]

Tyrosol

Phenoliccompo

und

MPP

(+)-indu

cedCA

THacells

PDmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia


TPprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

(i)activ

ationof

PI3K

Akt

signalling

pathway

[116]

Umbelliferone

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ursod

eoxycholic

acid

Second

arybileacids

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

SNP-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[74]

XyloketalB

Triterpenoid

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

eland

Caenorhabditiseleg

anso

fMPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[117]
















1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Pyruvate

Organicacid

Invitro

human

neurob

lasto

maS

K-N-SHcells

mod

elof

H2O

2-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[79]

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

elof

dopamine-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

ndarrp53

darrnu

clear

translo

catio

nof

NF-kapp

aBInhibitio

nof

them

itochon

drialapo

ptoticpathway

[80]

Quercetin

Biofl

avon

oid

Roteno

ne-in

ducedratP

Dmod

elMaintenance

ofmito

chon


ndarrRO

Sgeneratio

nmaintainmito

chon

drialm

embranep

otentia

l[108]

Invitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[109]

Rapamycin

Macrolid

e6-OHDA-

indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-9

darrcytochromec

release

Maintenance

ofmito

chon


ndarrlip

idperoxidatio

nuarrSO

DandGSH

-PX

[110]

Resveratrol

Polyph

enol

Invitro

prim

aryfib

roblastscultu

resfrom

patie

ntsw

ithparkin

mutations

(PARK

2)

Maintenance

ofmito

chon


nuarrcomplex

Iactivity

uarrcitrates

ynthasea

ctivity


ption

uarrmito

chon

drialA

TPprod

uctio

ndarrlactatec

ontent

[111]

Rosm

arinicacid

Polyph

enol

Invitro

MES

235do

paminergicc

ellsmod

elof

6-OHDA-

indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

n[112]

Salvianica

cidA

Polyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

MPP

(+)-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

x[113]

Salviano

licacid

BPo

lyph

enol

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

6-OHDA-

indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[114]


Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Sesamin

Lign

anIn

vitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[22]

Tetram

ethylpyrazine

Pyrazine

MPT

P-indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[115]

Tyrosol

Phenoliccompo

und

MPP

(+)-indu

cedCA

THacells

PDmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia


TPprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

(i)activ

ationof

PI3K

Akt

signalling

pathway

[116]

Umbelliferone

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ursod

eoxycholic

acid

Second

arybileacids

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

SNP-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[74]

XyloketalB

Triterpenoid

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

eland

Caenorhabditiseleg

anso

fMPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[117]
















1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Con

tinued

Com

poun

dClasso

fcom

poun

dParkinsonrsquos

mod

elMechanism

sRe

ferences

Sesamin

Lign

anIn

vitro

glial-n

euronalsystem

mod

elof

MPP

(+)-indu

cedPD

Maintenance

ofmito

chon


ndarrindu

ciblen

itricoxides

ynthasep

rotein

expressio

ndarrsuperoxide

radicals

[22]

Tetram

ethylpyrazine

Pyrazine

MPT

P-indu

cedratP

Dmod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa

xdarrcaspase-3

darrcytochromec

release

[115]

Tyrosol

Phenoliccompo

und

MPP

(+)-indu

cedCA

THacells

PDmod

el

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia


TPprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

(i)activ

ationof

PI3K

Akt

signalling

pathway

[116]

Umbelliferone

Cou

marin

MPT

P-indu

cedmiceP

Dmod

elInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3

[94]

Ursod

eoxycholic

acid

Second

arybileacids

Invitro

human

neurob

lasto

maS

H-SY5

Ycells

mod

elof

SNP-indu

cedPD

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2darrBa


darrcytochromec

release

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[74]

XyloketalB

Triterpenoid

Invitro

ratadrenalph

eochromocytom

a(PC

12)cellsmod

eland

Caenorhabditiseleg

anso

fMPP

(+)-indu

cedPD

Maintenance

ofmito

chon


nmaintainmito

chon

drialm

embranep

otentia

ldarrRO

Sgeneratio

nuarrglutathion

e

[117]
















1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of































1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






















1ndash40and A120573

























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





























Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Alzh

eimerrsquosdiseasea

ndmito

chon

dria-ta

rgeted

protectiv

ecom

poun

ds

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

17-120573-Estr

adiol

Estro

gen

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Acetyl-L-carnitin

eAminoacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Acteoside

Glycosid

eIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ndarrRO

Sprod

uctio

ndarrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l-2ratio

darrcaspase-3cle

avage

[181]

ASS234

Aminew

ithcomplex

structure

Invitro

A1205731ndash42-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrlevelsof

cleaved

caspases

3and9

darrlevelsof

proteolysedPA

RP[182]

Caffeine

Alkaloid

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Colostrinin

Polypeptide

Invitro

A120573-in

ducedhu

man

SH-SY5

YandratP

C12cells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialH

2O2prod

uctio

n[183]

Crud

ecaffeine

Alkaloid

Invitro

prim

aryneuron

sfrom

J20mou

selin

e

Maintenance

ofmito

chon


nuarrAT

Plevels

darrRO

Sprod

uctio

nInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ity

[184]

Cyclo

sporin

Amdash

Invitro


chon

driafro

mmAPP

-Ppifminus

minustransgenicmice

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

uarrCa

2+bu

fferin

gcapacity

[185]

D60


xantho

genate

Invitro

A1205731ndash42-in

ducediso

latedbrainmito

chon

driamod

el(fr

omgerbils)

Maintenance

ofmito

chon


ndarrlevelsof

proteincarbon

yls

darrlevelsof

protein-bo

undHNE

darrlevelsof

3-NT

darrCy

tCrelease

Maintenance

ofGSH

GSSGratio

uarrGSTG

Pxand

GRactiv

ities

[186]

DAPT

Com

plex

structure

ofbu

tyleste

rIn

vitro

N2aA

PP695andN2aA

PPsw

ecellsmod

elsMaintenance

ofmito

chon


nstabilizatio

nof

norm

alMMPandAT

Plevels

[187]

Dim

ebon

Tetrahydrocarboline

Invitro


osed

isolatedratb

rain

mito

chon

dria

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

[188]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Edaravon

ePy

razolin

one

Invitro

N2aSweΔ

9cells

mod

el

Maintenance

ofmito

chon


nuarrMMP

darrRO

Sprod

uctio

ndarrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCa

spase-3activ

ation

[173]

Ergothioneine

2-Mercaptoh

istidine

trim

ethylbetaine

Invitro

A12057325ndash35-in

ducedPC

12ratp

heochrom

ocytom

acells

mod

el

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrratio

BaxBc

l-XL

darrcaspase-3activ

ation

[189]

Gels

olin

Peptide

Invitro

A1205731ndash42-in


mod

elMaintenance

ofmito

chon


nincrease

inmito

chon

drialcom

plex

IVactiv

ity[19

0]

Genistein

Phytoestrogen

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrmito

chon

drialN

aK-AT

Pase

activ

ity[191]

GLP

-1(9-36)

amide

Peptide

Invitro

sliceso

fhippo

campu

sfrom

APP

PS1

mice

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialSOlevels

[192]

Glutathione

Tripeptid

eIn

vitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

GypenosideX

VII

Phytoestrogen

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

norm

alMMP

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ationandcle

avage

darrPA

RPcle

avage

[194]

JHX-

4HK-

2and

HK-

4mdash

Invitro

A120573-in

ducedhu

man

SH-SY5

Ycells

mod

elPreventio

nfro

mMnC

l 2-indu

cedlossof

mito

chon

drialactivity

[195]

Lipo

icacid

Organosulfur

compo

undderiv

edfro

moctano

icacid

Invivo

F344

ratm

odel

Resto

ratio

nof

intactmito

chon

drialm

orph

ologyand

preventio

nfro

mage-relatedmito

chon

driald

ecay

[180]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Invitro


cedmou

semicroglialB

V2cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

activ

ationof

Bcl-2

antia

poptoticpathways

darrBa

xmRN

Alevel

uarrBc

l-2expressio

ndarrcaspase-3activ

ity

[197]

Invitro


cedrath

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


nresto

ratio

nof

MMPloss

attenu

ationof

respira

tory

chaincomplexes

uarrAT

Plevels

[198]

Melaton

inHormon

eIn

vivo

APP

PS1

transgenicmice

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rates

uarrMMP

uarrAT

Plevels

[170]

Invivo

APP

swmicem

odel

Maintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialrespiratory

rate

maintenance

ofMMP

darrRO

Sprod

uctio

nuarrAT

Plevels

[169]

Invitro

isolatedmito

chon

driafro

mpostm

ortem

human

ADand

SFADbrains

Activ

ationof

mito

chon

drialaconitase

[179]

Invivo

APP

transgenicmicem

odel

Maintenance

ofmito

chon


nuarrSO

Dactiv

ityInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa


ns

[168]

Methylene

blue

Phenothiazine

Invivo

C57B

L6mice

Maintenance

ofmito

chon


nuarrmito

chon

drialcom

plex

IV(C

ytCoxidase)

activ

itydarrMAO

activ

ity

[199]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


norm

alizationin

mito

chon

drianu

mber

[200]

Mito

QMethanesulfo

nate

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invivo

3xTg

-ADmice

Maintenance

ofmito

chon


npreventio

nof

MMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

blockage

ofcaspases-37

activ

ation

[171]

Invivo

Caenorhabditiseleg

ansm

odeloverexpressin

ghu

man

A120573

peptides

Maintenance

ofmito

chon


ndarrdepletionof

mito

chon

driallipid

cardiolip

inProtectio

nof

complexes

IVandIo

fthe

ETC

[201]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Mito

chon

drial

divisio

ninhibitor1

(Mdivi-1)

Quinazolin

one

Invitro

A120573-in

ducedmou

seBV

-2cells

andprim

arymicroglial

cells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalmito

chon

drialfi

ssion

darrMMPloss

darrCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-3activ

ation

[182]

Invitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

N-Acetylcysteine

Aminoacid

deriv

ative


cedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

APP

PS-1m

ice

Ameliorationof

energy

levelsandmito

chon

drial-related

proteins

[202]

Invitro

fibroblastsfro

mADpatie

nts

Maintenance

ofmito

chon


ndarrNMP-indu

cedmito

chon

drialoxidativ

estre

ssInhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xandcaspase-9levels

[196]

Neuregulin

-1Peptide

Invitro

mod

elof

SH-SY5

Yhu

man

neurob

lasto

mac

ells

transfe

cted

with

C-term

inalfragmentsof

APP

Maintenance

ofmito

chon


ndarrMMPloss

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2expressio

n

[203]

Nicotinam

ide

Amide

Invivo

A1205731ndash42-in

ducedratm

odel

Upregulationof

mito

chon

drialfun

ction

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xlevels

[204]

Peroxiredo

xin3

Enzyme

Invivo

APP

transgenicmice(Tg

2576)a

ndAPP

Prdx3

transgenicmicem

odels

Maintenance

ofmito

chon


ndarrmito

chon

drialD

NAoxidation

uarractiv

ityof

mito

chon

drialcom

plexes

Iand

IV[205]

Peroxiredo

xin6

Enzyme

Invitro

A12057325ndash35-in

ducedPC

12cells

mod

el

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ation

darrPA

RPactiv

ation

darrBc

l-2andBa

xdysregulations

[206]


Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

Prob

ucol

mdashIn

vitro

cybrid

cells

mod

el(m

tDNA-

depleted

neuron

alSH

5Y5Y

cells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Maintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

nuarrMMP

uarrmito

chon


uarrCy

tCoxidasea

ctivity

uarrSO

Dactiv

ityuarrAT

Plevels

darrim

paire

dmito

chon

drialfi

ssionandfusio

ndynamics

[174]

Puerarin

Phytoestrogen

Invivo

A1205731ndash42-in

ducedratm

odel

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspase-9activ

ityandmRN

Alevels

[207]

Invitro

cybridcells

mod

el(m

tDNA-

depleted

neuron

alSH

-5Y5

Ycells

transfe

cted

with

plateletmito

chon

driafro

mADpatie

nt)

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

uarrBc

l-2levels

darrBa

xexpressio

ndarrcaspase-3activ

ity

[208]

R(+)

andS(minus)

pram

ipexoles

mdashIn

vitro

A12057325ndash35-in

ducedSH

-SY5

Yhu

man

neurob

lasto

mac

ells

mod

el

Maintenance

ofmito

chon


ninhibitio

nof

mPT

Pop

ening

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrcaspases

3and9activ

ations

[209]

Resistin

Adipok

inep

rotein

Invitro

mou

seN2aSweΔ

9cells

(N2a

cells

transfe

cted

with

Sw-APP

mutantand

presenilinexon

9deletio

nmutant)

Maintenance

ofmito

chon


nuarrAT

Plevels

uarrMMP

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrBa

xBc

l2ratio

darrCy

tCrelease

darrcaspase-3activ

ation

[210]

Resveratrol

Polyph

enol

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

nSalicylate

Sulin

dacs

ulfid

eIndo

methacin

Ibup

rofen

R-flu

rbiprofen

NSA

IDs

Invitro

A1205731ndash42-a


ducedratcerebellarg

ranu

lecells

andcorticalneuron

smod

el

Maintenance

ofmito

chon


nuarrMMP

darrmito

chon

drialC

a2+overload

darrCy

tCrelease

[172]


ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















ble2Con

tinued

Com

poun

dClasso

fcom

poun

dADmod

elMechanism

effect

References

SS31

Peptide

Invitro

A12057325ndash35-in

ducedC5

7BL6miceh

ippo

campaln

eurons

mod

el

Maintenance

ofmito

chon


ndarrlevelsof

mito

chon

drialfi

ssionproteins

(Drp1

Fis1)matrix

protein

andCy

pDuarrnu

mbero

fhealth

yandintactmito

chon

dria

Resto

ratio

nof

mito

chon

drialtranspo

rt

[162]

Invitro

A120573-in

ducedmou

seneurob

lasto

maN

2acells

mod

el

Maintenance

ofmito

chon


ndarrabno

rmalexpressio

nof

peroxiredo

xins

and

mito

chon


Normalizationin

mito

chon

drianu

mber

[200]

Invivo

A120573PP

transgenicmice

Maintenance

ofmito

chon


ndarrCy

pDexpressio

n

Invitro

Tg2576

micep

rimaryneuron

sMaintenance

ofmito

chon


nresto

ratio

nof

mito

chon

drialtranspo

rtdarrpercentage

ofdefectivem

itochon

dria

[211]

Thym

oquino

neBe

nzoq

uino

neIn

vitro

A12057325ndash35-in

ducedPC

12cells

mod

elMaintenance

ofmito

chon


nuarrMMP

[212]

Invitro

A1205731ndash42-in

ducedprim

aryratn

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[213]

Tournefolic

acid

BPo

lyph

enol


ducedratcortic

alneuron

smod

el

Maintenance

ofmito

chon


ndarrmito

chon

drialC

a2+levels

delay

inCy

tCrelease

Inhibitio

nof

them

itochon

drialapo

ptoticpathway

darrtBid

levels

[214]

Trolox

Analogof

vitamin

EIn

vitro

dentateg

ranu

lecells

from

transgenicmou

seADmod

el(Tg2576)

Maintenance

ofmito

chon


nscavenging

ofmito

chon

drialSO

resto

ratio

nof

Ca2+cle

arance

uarrMMP

[215]

UPF

1and

UPF

17Peptides

Mito

chon

drialfractionof

postm

ortem

human

ADbrains

uarrMito

chon

drialM

n-SO

Dactiv

ity[191]

Vitamin

CVitamin

Invitro

A120573-in

ducedhu

man

HCN

-1Acells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialm

embraned

epolarization

[193]

Invivo

5XFA

DKn

ockout-tr

ansgenicmicem

odel

Maintenance

ofmito

chon


npreventio

nof

abno

rmalmito

chon

drialm

orph

olog

y[216]

Wy-14463

(peroxiso

me

proliferator)

mdashIn

vitro

A1205731ndash40-in

ducedprim

aryrath

ippo

campaln

eurons

mod

elMaintenance

ofmito

chon


nuarrMMP

[217]

Zeolite

mdashIn

vitro

H2O

2-indu

cedSH

-SY5

Ycells

mod

elMaintenance

ofmito

chon


ndarrmito

chon

drialR

OSprod

uctio

n[218]

Invivo

APP

swePS1dE

9transgenicmicem

odel

Sign

ificant

increase

inSO

Dactiv

ityET

Celectro

ntransportchain

MMP

mito

chon

drialmem

branepo

tentialCy

tCc

ytochrom

eC

SOs

uperoxide

SODs

uperoxidedism

utase

SwAPP

Swedish


ROS

reactiv

eoxygen

species4H

NE

4-hydroxy-2-no

nenalAC

hEa

cetylch

olineesteraseG

SHg

lutathioneG

Rglutathion

eredu

ctase

GPx

glutathione

peroxidaseS

FADS

wedish

Familial

Alzh

eimerrsquosdisease

MAO

mon

oamineoxidasetBidB

H3interactingdo

maindeathagon

istB

akB

cl-2agon

istkiller1mPT

Pmito

chon

drialp


reC

ypDcyclosporineDN

MP

N-m

ethylp

rotopo

rphyrin

SP-

04d

imethyl-c

arbamicacid


iperazine-1-c

arbo

nyl)-ph

enyl

esterSP-04m

4-(4-ethyl-p


tan-1-o

neC

CCP

carbon

ylcyanide

3-chloroph

enylhydrazon

eFC

CPcarbo

nylcyanide

p-trifluo

rometho


phenylarsineo

xidePARP

poly-ADP-rib

osylpo

lymerasemtD

NAm

itochon

drialD

NAP

ar-4prosta

teapop

tosis

respon

se-43-NT

3-nitro

tyrosin

eGSH

redu

cedglutathion

eGSSGoxidized

glutathion

eGST

glutathion

e-S-transfe

raseGPx

glutathion

eperoxidaseGR

glutathion

eredu

ctase

ASS234

N-((5-(3-(1-

benzylpiperid

in-4-yl)p

ropo

xy)-1-m

ethyl-1H-in

dol-2

-yl)m

ethyl)-N-m

ethylprop-2-yn

-1-am

ineAPP

amyloidprecursorp

roteinA120573120573

amyloidNSA

IDsno



III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















III

IIIIV

V

Mitochondrial DNA

Peroxiredoxin-3





DNA damage



Apoptosis


probucol zeolite




MitoQ



uarr ROS

uarr ROS

uarr ROS





Ca2+


uarr Cytosolic Ca2+

































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of







































Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Acknowledgment


References
















































































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






























































































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





























































60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






























60(OH)












































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of








































































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















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Review Article Mitochondria-Targeted Protective Compounds in …downloads.hindawi.com/journals/omcl/2015/408927.pdf · 2019-07-31 · Review Article Mitochondria-Targeted Protective