变构调节
锡尔图因
NAD+激酶
西妥因1
SIRT2
白藜芦醇
酶
生物化学
生物
化学
药理学
计算生物学
基因
下调和上调
作者
David Sinclair,Leonard Guarente
出处
期刊:Annual Review of Pharmacology and Toxicology
[Annual Reviews]
日期:2011-03-03
卷期号:54 (1): 363-380
被引量:206
标识
DOI:10.1146/annurev-pharmtox-010611-134657
摘要
The mammalian sirtuins (SIRT1-7) are NAD(+)-dependent lysine deacylases that play central roles in cell survival, inflammation, energy metabolism, and aging. Members of this family of enzymes are considered promising pharmaceutical targets for the treatment of age-related diseases including cancer, type 2 diabetes, inflammatory disorders, and Alzheimer's disease. SIRT1-activating compounds (STACs), which have been identified from a variety of chemical classes, provide health benefits in animal disease models. Recent data point to a common mechanism of allosteric activation by natural and synthetic STACs that involves the binding of STACs to a conserved N-terminal domain in SIRT1. Compared with polyphenols such as resveratrol, the synthetic STACs show greater potency, solubility, and target selectivity. Although considerable progress has been made regarding SIRT1 allosteric activation, key questions remain, including how the molecular contacts facilitate SIRT1 activation, whether other sirtuin family members will be amenable to activation, and whether STACs will ultimately prove safe and efficacious in humans.
科研通智能强力驱动
Strongly Powered by AbleSci AI