Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.
Chembiochem. 2011 Jan 24;12(2):281-9. doi: 10.1002/cbic.201000434. Epub 2010 Nov 9.
SIRT1 is a member of the Sir2 family of NAD(+)-dependent protein deacetylases. The central role of SIRT1 in multiple metabolic and age-related pathways has pushed SIRT1 to the forefront to discover small-molecule activators. Promising compounds, including resveratrol and SRT1720 have been reported, however, whether these compounds are direct activators and the mechanism by which they activate remains poorly defined. This review examines the current debate surrounding purported activators, and will focus on the assays used in screening compounds, sirtuin catalysis, and the mechanistic basis for their actions. We discuss the potential pathways of SIRT1 activation that could be exploited for the development of novel therapeutics for treating type II diabetes, neurodegeneration, and diseases associated with aging.
SIRT1 是 NAD(+) 依赖的蛋白去乙酰化酶 Sir2 家族的一员。SIRT1 在多种代谢和与年龄相关的途径中的核心作用将 SIRT1 推向了发现小分子激活剂的前沿。已经报道了有前途的化合物，包括白藜芦醇和 SRT1720，然而，这些化合物是否是直接的激活剂以及它们激活的机制仍未得到很好的定义。这篇综述审查了围绕所谓的激活剂的当前争论，并将重点讨论用于筛选化合物、去乙酰化酶催化以及它们作用的机制基础的测定方法。我们讨论了 SIRT1 激活的潜在途径，这些途径可用于开发治疗 II 型糖尿病、神经退行性疾病和与衰老相关疾病的新型治疗药物。
