Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy.
Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Italy.
Molecules. 2022 Sep 1;27(17):5641. doi: 10.3390/molecules27175641.
Sirtuins are NAD-dependent deac(et)ylases with different subcellular localization. The sirtuins' family is composed of seven members, named SIRT-1 to SIRT-7. Their substrates include histones and also an increasing number of different proteins. Sirtuins regulate a wide range of different processes, ranging from transcription to metabolism to genome stability. Thus, their dysregulation has been related to the pathogenesis of different diseases. In this review, we discussed the pharmacological approaches based on sirtuins' modulators (both inhibitors and activators) that have been attempted in in vitro and/or in in vivo experimental settings, to highlight the therapeutic potential of targeting one/more specific sirtuin isoform(s) in cancer, neurodegenerative disorders and type 2 diabetes. Extensive research has already been performed to identify SIRT-1 and -2 modulators, while compounds targeting the other sirtuins have been less studied so far. Beside sections dedicated to each sirtuin, in the present review we also included sections dedicated to pan-sirtuins' and to parasitic sirtuins' modulators. A special focus is dedicated to the sirtuins' modulators identified by the use of virtual screening.
Sirtuins 是 NAD 依赖性去乙酰化酶，具有不同的亚细胞定位。Sirtuins 家族由 7 个成员组成，分别命名为 SIRT-1 至 SIRT-7。它们的底物包括组蛋白，以及越来越多的不同蛋白质。Sirtuins 调节广泛的不同过程，从转录到代谢到基因组稳定性。因此，它们的失调与多种疾病的发病机制有关。在这篇综述中，我们讨论了基于 Sirtuins 调节剂（抑制剂和激活剂）的药理学方法，这些方法已经在体外和/或体内实验环境中进行了尝试，以强调针对癌症、神经退行性疾病和 2 型糖尿病中的一个/多个特定 Sirtuin 同工型的治疗潜力。已经进行了广泛的研究来鉴定 SIRT-1 和 -2 调节剂，而迄今为止针对其他 Sirtuins 的化合物研究较少。除了专门针对每个 Sirtuin 的部分外，本综述还包括专门针对泛 Sirtuins 和寄生虫 Sirtuins 调节剂的部分。特别关注使用虚拟筛选鉴定的 Sirtuins 调节剂。
