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Catalysis and Mechanistic Insights into Sirtuin Activation
Author(s) -
DittenhaferReed Kristin E.,
Feldman Jessica L.,
Denu John M.
Publication year - 2011
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201000434
Subject(s) - sirtuin , neurodegeneration , nad+ kinase , mechanism (biology) , resveratrol , sirtuin 1 , sirt2 , chemistry , computational biology , biology , microbiology and biotechnology , biochemistry , enzyme , medicine , gene , downregulation and upregulation , disease , philosophy , epistemology , pathology
Abstract 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.