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Sirtuin 2 inhibitors rescue α-synuclein-mediated toxicity in models of Parkinson's disease

被引：880
作者：
Outeiro, Tiago Fleming
Kontopoulos, Eirene
Altmann, Stephen M.
Kufareva, Irina
Strathearn, Katherine E.
Amore, Allison M.
Volk, Catherine B.
Maxwell, Michele M.
Rochet, Jean-Christophe
McLean, Pamela J.
Young, Anne B.
Abagyan, Ruben
Feany, Mel B.
Hyman, Bradley T.
Kazantsev, Aleksey G.
机构：
[1] Harvard Univ, Sch Med, MassGen Inst Neurodegenerat Dis, MGH, Charlestown, MA 02129 USA
[2] Harvard Univ, Sch Med, Alzheimers Res Unit, MGH, Charlestown, MA 02129 USA
[3] Harvard Univ, Sch Med, Boston, MA 02115 USA
[4] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[5] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[6] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA
来源：
SCIENCE | 2007年 / 317卷 / 5837期
关键词：
DROSOPHILA MODEL; LEWY BODIES; PROTEIN; AGGREGATION; DEACETYLASE; ACETYLATION; SUPPRESSION; HUNTINGTONS; SIRT2; HDAC6;
D O I：
10.1126/science.1143780
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a role in aging. We identified a potent inhibitor of sirtuin 2 ( SIRT2) and found that inhibition of SIRT2 rescued alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued alpha-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging.
引用
收藏
页码：516 / 519
页数：4
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