将SIRT2与帕金森病联系起来。

Linking SIRT2 to Parkinson's disease.

作者信息

Garske Adam L, Smith Brian C, Denu John M

机构信息

Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

出版信息

ACS Chem Biol. 2007 Aug 17;2(8):529-32. doi: 10.1021/cb700160d.

DOI:10.1021/cb700160d

PMID:17708669

Abstract

A recent study has identified selective inhibitors of the human silent information regulator 2 NAD (+)-dependent protein deacetylase, SIRT2, and has shown that these compounds protect against alpha-synuclein-mediated toxicity in cellular models of Parkinson's disease. The inhibitors were found to ameliorate dopaminergic cell death in vitro and in a Drosophila model of Parkinson's disease. Although the molecular mechanism of action is unclear, the compounds may function by promoting the formation of enlarged inclusion bodies, which are suggested to provide a cell-survival advantage.

摘要

最近的一项研究鉴定出了人类沉默信息调节因子2（SIRT2）的选择性抑制剂，它是一种依赖烟酰胺腺嘌呤二核苷酸（NAD+）的蛋白质脱乙酰酶，研究表明这些化合物在帕金森病的细胞模型中可抵御α-突触核蛋白介导的毒性。这些抑制剂在体外以及帕金森病果蝇模型中均能改善多巴胺能细胞死亡。尽管作用的分子机制尚不清楚，但这些化合物可能通过促进形成增大的包涵体发挥作用，有人认为这些包涵体可提供细胞生存优势。