The Sirtuin 2 Inhibitor AK-7 Is Neuroprotective in Huntington's Disease Mouse Models

被引：171

作者：

Chopra, Vanita ^{[1
]}

Quinti, Luisa ^{[1
]}

Kim, Jinho ^{[2
,3
,4
,5
]}

Vollor, Lorraine ^{[1
]}

Narayanan, K. Lakshmi ^{[1
]}

Edgerly, Christina ^{[2
,3
,4
,5
]}

Cipicchio, Patricia M. ^{[2
,3
,4
,5
]}

Lauver, Molly A. ^{[2
,3
,4
,5
]}

Choi, Soo Hyuk ^{[6
]}

Silverman, Richard B. ^{[6
]}

Ferrante, Robert J. ^{[2
,3
,4
,5
]}

Hersch, Steven ^{[1
]}

Kazantsev, Aleksey G. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA

[2] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15213 USA

[3] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA

[4] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15213 USA

[5] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr GR H 00, Pittsburgh, PA 15206 USA

[6] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chem Life Proc Inst, Dept Mol Biosci,Dept Chem, Evanston, IL 60208 USA

来源：

CELL REPORTS | 2012年 / 2卷 / 06期

关键词：

DEACETYLASE; PROTEIN; MICE;

D O I：

10.1016/j.celrep.2012.11.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Inhibition of sirtuin 2 (SIRT2) deacetylase mediates protective effects in cell and invertebrate models of Parkinson's disease and Huntington's disease (HD). Here we report the in vivo efficacy of a brain-permeable SIRT2 inhibitor in two genetic mouse models of HD. Compound treatment resulted in improved motor function, extended survival, and reduced brain atrophy and is associated with marked reduction of aggregated mutant huntingtin, a hallmark of HD pathology. Our results provide preclinical validation of SIRT2 inhibition as a potential therapeutic target for HD and support the further development of SIRT2 inhibitors for testing in humans.

引用

页码：1492 / 1497

页数：6

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