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p35
Akt CDK5
Calpain
GSK-3α/βTau
AICDAICD
APP
Casp-3,-9
APP
NMDARNMDAR
sAPPβsAPPα Aβ40/42
AMPARAMPAR AcetylcholineReceptors:
nAChRmAChR
GlucoseTransporters
GlucoseTransporters
DR6
N-APP
Apoptosis
Apoptosis
Apoptosis DestabilizedMicrotubules
Hyperphosphorylation of Tau
Activation of PKC, PKA, Erk2
Casp-6
Membrane Damage
Oxidative Stress
ROS Formation
MicrogliaActivation
Inflammatory Cytokines
Lipid Peroxidation
Amyloid Plaques Aβ Misfolding, Aggregation
ROS Formation
p53, Bad,Bax productionand activation
Normal State Alzheimer’s Disease State
Neurofibrillary Tangles
β-SecretaseAPP
APPIntracellular
Domain
PEN-2Aph
NicastrinPresenilin
Nuclear translocationTranscriptional regulation
Normal Axon
Pruning
Aberrant Neuronal Death
Increased Neuronal Survival,Neutrite Outgrowth,
Synaptic sAPPα Plasticity,Cell Adhesion
α-Secretase
γ-Secretase
γ-Secretase
p25
Ca2+Na+Glc
nAChRmAChR
© 2009 – 2010 Cell Signaling Technology, Inc. Amyloid Plaque and Neurofibrillary Tangle Formation in Alzheimer’s Disease • created July 2009 • revised November 2010
Amyloid Plaque and Neurofibrillary Tangle Formation in Alzheimer’s Disease
www.cellsignal.com
Direct Stimulatory ModificationKinase
Phosphatase
Caspase
Receptor
Cyclin, pro-apoptotic
Enzyme
pro-survival
GAP / GEF
GTPase
G-protein, ribosomal subunit
Transcription Factor
Transcriptional Stimulation
Transcriptional Inhibition
Translocation
Separation of Subunits or Cleavage Products
Joining of Subunits
Direct Inhibitory Modification
Multistep Stimulatory Modification
Multistep Inhibitory Modification
Tentative Stimulatory Modification
Tentative Inhibitory Modification
Signaling Pathways Key
www.cellsignal.com
© 2003 - 2010 Cell Signaling Technology, Inc.
Acetylase
Deacetylase