NAD^+依赖的组蛋白去乙酰化酶sirtuins及其调节剂的研究进展

Advances in NAD^+ -dependent Histone Deacetylases, Sirtuins, and Their Modulators

sirtuins是NAD+依赖的组蛋白去乙酰化酶,属于组蛋白去乙酰化酶的第Ⅲ亚族。其功能与基因表达、代谢调控、细胞凋亡和生存、DNA修复、炎症、神经保护和长寿密切相关。sirtuins的调控对人类疾病有重要治疗作用,因此研究影响该靶点功能的小分子调节剂成为当前药物研究的热点领域之一。本文综述了能激活或抑制该酶的活性化合物,并讨论其用于临床的潜在意义。

Sirtuins belong to the third class of histone deacetylases, which are dependent on NAD~ for activity. The functions are related to gene expression, metabolic control, apoptosis and cell survival, DNA repair, inflammation, neuroprotection and longevity. Because the regulation of the human sirtuins plays an important therapeutic role in diseases, the research of small molecule modulators impacting target function becomes one of the hot fields of pharmaceutical research. This review lists some active compounds which can activate or inhibit the enzyme, and discusses the potential implications for clinical practice.