Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
Department of Pharmaceutical Chemistry, Martin-Luther Universität Halle-Wittenberg, Halle/Saale, Germany.
Med Res Rev. 2018 Jan;38(1):147-200. doi: 10.1002/med.21436. Epub 2017 Jan 17.
Sirtuins are NAD -dependent protein deacylases that cleave off acetyl, as well as other acyl groups, from the ε-amino group of lysines in histones and other substrate proteins. Seven sirtuin isotypes (Sirt1-7) have been identified in mammalian cells. As sirtuins are involved in the regulation of various physiological processes such as cell survival, cell cycle progression, apoptosis, DNA repair, cell metabolism, and caloric restriction, a dysregulation of their enzymatic activity has been associated with the pathogenesis of neoplastic, metabolic, infectious, and neurodegenerative diseases. Thus, sirtuins are promising targets for pharmaceutical intervention. Growing interest in a modulation of sirtuin activity has prompted the discovery of several small molecules, able to inhibit or activate certain sirtuin isotypes. Herein, we give an update to our previous review on the topic in this journal (Schemies, 2010), focusing on recent developments in sirtuin biology, sirtuin modulators, and their potential as novel therapeutic agents.
去乙酰化酶 Sirtuins 是 NAD 依赖性蛋白去酰基酶，能够从组蛋白和其他底物蛋白中赖氨酸ε-氨基上切割掉乙酰基以及其他酰基。在哺乳动物细胞中已经鉴定出 7 种 Sirtuins 同工型（Sirt1-7）。由于 Sirtuins 参与调节多种生理过程，如细胞存活、细胞周期进程、细胞凋亡、DNA 修复、细胞代谢和热量限制，因此它们的酶活性失调与肿瘤、代谢、感染和神经退行性疾病的发病机制有关。因此，Sirtuins 是药物干预的有前途的靶点。人们对 Sirtuins 活性的调节越来越感兴趣，这促使人们发现了几种能够抑制或激活某些 Sirtuins 同工型的小分子。在此，我们在本刊之前的综述（Schemies，2010）的基础上进行了更新，重点介绍了 Sirtuins 生物学、Sirtuins 调节剂的最新进展及其作为新型治疗药物的潜力。
