Advances in Characterization of Human Sirtuin Isoforms: Chemistries, Targets and Therapeutic Applications
Authors: Cen, Y.; Y. Youn, D.; A. Sauve, A.
Source: Current Medicinal Chemistry, Volume 18, Number 13, May 2011 , pp. 1919-1935(17)
Publisher: Bentham Science Publishers
Abstract:Since the discovery in 2000 that the yeast sirtuin called “Sir2” catalyzes NAD+ dependent histone deacetylation, a wave of research has focused on evaluating the biochemical and biological functions of sirtuins. Sirtuins are activated by low calorie diets in numerous organisms and are found throughout biology in species from archaea to humans. There are seven human sirtuin isoforms called SIRT1-SIRT7. The biochemical functions of SIRT1, SIRT2, SIRT3, SIRT5 and SIRT6 have been reported and NAD+ dependent deacetylase activities confirmed. In some instances the biological target substrates for each isoform have been identified, helping to connect distinct biological processes to sirtuin regulation. This knowledge has informed potential drug design strategies that target distinct sirtuin isoforms. This review presents current knowledge of biochemical activities of SIRT1-7 in humans and the biological consequences of these sirtuin activities. Regulatory principles that govern sirtuin deacetylation activity in cells are discussed as well as strategies for how sirtuins can be targeted by small molecules. Finally, this review updates research on pharmacologic sirtuin activation and allostery on sirtuins and considers new developments for detection and isolation of sirtuins in complex mixtures.
Document Type: Research Article
Publication date: May 2011
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.