Progeria - Daniela Pereira

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ProgeriasHutchinson-Gilford Progeria Syndrome

Meeting on The Future of Aging

Daniela Pereira

terça-feira, 19 de Abril de 2011



Daniela Pereira

MBCM 2010/2011

Hutchinson-GilfordProgeriaSyndrome(HGPS)

Daniela Pereira

MBCM 2010/2011

!"#$%

!"#$%&'()$(*+",%

-*.'#-$#%

/,+$#"0'(.%*(%+1$%

234/%)$($%

5$"+1%6$7'#$%+1$%

")$%'7%89%

:1"()$.%+;<*&",%'7%

',-%")$%Lobula'onofthenuclearmembrane

Diminishedreplica'onpotencial

SlowDNAdamageresponse

Abnormalchroma'norganiza'on

Deckeretal(2009)MechAgeingDev,130,377-383.




Daniela Pereira

MBCM 2010/2011

Prematureagingsymptomes

Lipodystrophy

Alopecia

Joint contractures

Pereiraetal(2008)MechAgeingDev129,449-459.




Daniela Pereira

MBCM 2010/2011

Structureandfunc<onofthenuclearlamina

Daniela Pereira

MBCM 2010/2011

Cou'nhoetal(2009)ImmunAgeing,6:p.4.




Daniela Pereira

MBCM 2010/2011

BiogenesisoflaminA







Daniela Pereira

MBCM 2010/2011

Potencialmechanismsofdisease





Daniela Pereira

MBCM 2010/2011

WormanAndBonne(2007)ExpCellRes313,2121-2133.

Structureandfunc<onofthenuclearlamina




Daniela Pereira

MBCM 2010/2011

Howmanydifferentmuta<onsleadtomanydiseases?





Daniela Pereira

MBCM 2010/2011

Howmanydifferentmuta<onsinLMNAleadtomanydiseases?





Daniela Pereira

MBCM 2010/2011

Howmanydifferentmuta<onsleadtomanydiseases?





Daniela Pereira

MBCM 2010/2011Constan'nescuetal(2010)ExpCellRes316,2747-2759. Daniela Pereira

MBCM 2010/2011

NuclearmorphologyandlevelsofDSBs

Research Article

Defective DSB repair correlates with abnormal nuclear morphology and is improved with FTI treatment in

Hutchinson-Gilford progeria syndrome fibroblasts

Dan Constantinescub,c , Antonei B. Csokad, Christopher S. Navaraa,c , Gerald P. Schattena,b,c,

aDivision of Developmental and Regenerative Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences,

University of Pittsburgh, Pittsburgh, PA 15260, USAbDepartment of Cell Biology-Physiology, University of Pittsburgh, Pittsburgh, PA 15260, USAcPittsburgh Development Center, Magee-Women's Research Institute, University of Pittsburgh, Pittsburgh, PA 15260, USAdDivision of Geriatrics, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15260, USA

E X P E R I M E N T A L C E L L R E S E A R C H 3 1 6 ( 2 0 1 0 ) 2 7 4 7 – 2 7 5 9

a v a i l a b l e a t w w w . s c i e n c e d i r ec t . c o m

w w w . e l s e v i e r . c o m / l o c a t e / y e x c r




Daniela Pereira

MBCM 2010/2011Constan'nescuetal(2010)ExpCellRes316,2747-2759. Daniela Pereira

MBCM 2010/2011

NuclearmorphologyandlevelsofDSBs




Daniela Pereira

MBCM 2010/2011

Telomerelength

Deckeretal(2009)MechAgeingDev,130,377-383.

Telomere length in Hutchinson-Gilford Progeria Syndrome

Michelle L. Decker a,b, Elizabeth Chavez a, Irma Vulto a, Peter M. Lansdorp a,c,*a Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, Canadab Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canadac Division of Hematology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada

Mechanisms of Ageing and Development 130 (2009) 377–383

Contents lists available at ScienceDirect

Mechanisms of Ageing and Development

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / m e c h a g e d e v

• no chromosomal abormalities• no translocations

• no aneuploidy




Daniela Pereira

MBCM 2010/2011Deckeretal(2009)MechAgeingDev,130,377-383. Daniela Pereira

MBCM 2010/2011

TelomerelengthandexpressionofLMNA




Daniela Pereira

MBCM 2010/2011

LaminsinDNAreplica<on

Dechatetal(2008)Genes&development22,832-853.

10.1101/gad.1652708Access the most recent version at doi:2008 22: 832-853Genes Dev.

Thomas Dechat, Katrin Pfleghaar, Kaushik Sengupta, et al. function of the nucleus and chromatinNuclear lamins: major factors in the structural organization and




Daniela Pereira

MBCM 2010/2011

Mechanismofmodifiedproteinaccumula<on

Viterietal(2010)MechAgeingDev131,2-8.

Effect of progerin on the accumulation of oxidized proteins in fibroblasts fromHutchinson Gilford progeria patients

Gabriela Viteri, Youn Wook Chung, Earl R. Stadtman1,2

Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8012, USA

Mechanisms of Ageing and Development 131 (2010) 2–8

Contents lists available at ScienceDirect

Mechanisms of Ageing and Development

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m/ l o c a t e / m e c h a g e d e v




Daniela Pereira

MBCM 2010/2011Koshimizuetal(2011)PloSone6,e17688. Daniela Pereira

MBCM 2010/2011

Tostudyprogeriaandlaminopathies

Embryonic Senescence and Laminopathies in aProgeroid Zebrafish Model

Eriko Koshimizu1,2, Shintaro Imamura1¤a, Jie Qi1,5¤b, Jamal Toure1, Delgado M. Valdez Jr.5,

Christopher E. Carr3, Jun-ichi Hanai4, Shuji Kishi1,5*

1 Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Graduate School of Marine Science and Technology,

University of Marine Science and Technology, Tokyo, Japan, 3 Department of Earth, Atmospheric and Planetary Sciences, Massachusetts Institute of Technology,

Cambridge, Massachusetts, United States of America, 4 Division of Nephrology, Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel

Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America, 5 Department of Metabolism and Aging, The Scripps ResearchInstitute, Jupiter, Florida, United States of America

Zebrafish models to study human premature aging disorder.




Daniela Pereira

MBCM 2010/2011

TakeHomeMessage

Smallperturba<onsinmetabolismoflaminAaresufficienttocauseprominent

nucleardefectsandresultinaprogeroidphenotype.

SuggestthatlaminAmetabolism

mayplayanimportantrolein

humanaging.




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Progeria - Daniela Pereira