progeria - daniela pereira
TRANSCRIPT
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 1/20
ProgeriasHutchinson-Gilford Progeria Syndrome
Meeting on The Future of Aging
Daniela Pereira
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 2/20
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.
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 3/20
Daniela Pereira
MBCM 2010/2011
Prematureagingsymptomes
Lipodystrophy
Alopecia
Joint contractures
Pereiraetal(2008)MechAgeingDev129,449-459.
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 4/20
Daniela Pereira
MBCM 2010/2011
Structureandfunc<onofthenuclearlamina
Daniela Pereira
MBCM 2010/2011
Cou'nhoetal(2009)ImmunAgeing,6:p.4.
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 5/20
Daniela Pereira
MBCM 2010/2011
BiogenesisoflaminA
Cou'nhoetal(2009)ImmunAgeing,6:p.4.
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 6/20
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 7/20
Daniela Pereira
MBCM 2010/2011
Potencialmechanismsofdisease
Cou'nhoetal(2009)ImmunAgeing,6:p.4.
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 8/20
Daniela Pereira
MBCM 2010/2011
WormanAndBonne(2007)ExpCellRes313,2121-2133.
Structureandfunc<onofthenuclearlamina
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 9/20
Daniela Pereira
MBCM 2010/2011
Howmanydifferentmuta<onsleadtomanydiseases?
WormanAndBonne(2007)ExpCellRes313,2121-2133.
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 10/20
Daniela Pereira
MBCM 2010/2011
Howmanydifferentmuta<onsinLMNAleadtomanydiseases?
WormanAndBonne(2007)ExpCellRes313,2121-2133.
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 11/20
Daniela Pereira
MBCM 2010/2011
Howmanydifferentmuta<onsleadtomanydiseases?
WormanAndBonne(2007)ExpCellRes313,2121-2133.
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 12/20
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
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 13/20
Daniela Pereira
MBCM 2010/2011Constan'nescuetal(2010)ExpCellRes316,2747-2759. Daniela Pereira
MBCM 2010/2011
NuclearmorphologyandlevelsofDSBs
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 14/20
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
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 15/20
Daniela Pereira
MBCM 2010/2011Deckeretal(2009)MechAgeingDev,130,377-383. Daniela Pereira
MBCM 2010/2011
TelomerelengthandexpressionofLMNA
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 16/20
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
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 17/20
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
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 18/20
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.
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 19/20
Daniela Pereira
MBCM 2010/2011
TakeHomeMessage
Smallperturba<onsinmetabolismoflaminAaresufficienttocauseprominent
nucleardefectsandresultinaprogeroidphenotype.
SuggestthatlaminAmetabolism
mayplayanimportantrolein
humanaging.
terça-feira, 19 de Abril de 2011
8/6/2019 Progeria - Daniela Pereira
http://slidepdf.com/reader/full/progeria-daniela-pereira 20/20
THANKSFORYOURATTENTION