Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China; School of Medicine Jiangsu University, Zhenjiang, Jiangsu, China.
School of Medicine Jiangsu University, Zhenjiang, Jiangsu, China.
Biomed Pharmacother. 2024 May;174:116481. doi: 10.1016/j.biopha.2024.116481. Epub 2024 Mar 24.
Sirtuins (SIRTs) represent a class of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that exert a crucial role in cellular signal transduction and various biological processes. The mammalian sirtuins family encompasses SIRT1 to SIRT7, exhibiting therapeutic potential in counteracting cellular aging, modulating metabolism, responding to oxidative stress, inhibiting tumors, and improving cellular microenvironment. These enzymes are intricately linked to the occurrence and treatment of diverse pathological conditions, including cancer, autoimmune diseases, and cardiovascular disorders. Given the significance of histone modification in gene expression and chromatin structure, maintaining the equilibrium of the sirtuins family is imperative for disease prevention and health restoration. Mounting evidence suggests that modulators of SIRTs play a crucial role in treating various diseases and maintaining physiological balance. This review delves into the molecular structure and regulatory functions of the sirtuins family, reviews the classification and historical evolution of SIRTs modulators, offers a systematic overview of existing SIRTs modulation strategies, and elucidates the regulatory mechanisms of SIRTs modulators (agonists and inhibitors) and their clinical applications. The article concludes by summarizing the challenges encountered in SIRTs modulator research and offering insights into future research directions.
Sirtuins(SIRTs)是一类依赖烟酰胺腺嘌呤二核苷酸(NAD+)的蛋白去乙酰化酶,在细胞信号转导和各种生物学过程中发挥着关键作用。哺乳动物的 Sirtuins 家族包括 SIRT1 至 SIRT7,它们在抵抗细胞衰老、调节代谢、应对氧化应激、抑制肿瘤和改善细胞微环境方面具有治疗潜力。这些酶与多种病理状况的发生和治疗密切相关,包括癌症、自身免疫性疾病和心血管疾病。鉴于组蛋白修饰在基因表达和染色质结构中的重要性,维持 Sirtuins 家族的平衡对于疾病预防和健康恢复至关重要。越来越多的证据表明,SIRTs 的调节剂在治疗各种疾病和维持生理平衡方面发挥着重要作用。本综述深入探讨了 Sirtuins 家族的分子结构和调节功能,回顾了 SIRTs 调节剂的分类和历史演变,系统概述了现有的 SIRTs 调节策略,并阐明了 SIRTs 调节剂(激动剂和抑制剂)的调节机制及其临床应用。文章最后总结了 SIRTs 调节剂研究中遇到的挑战,并对未来的研究方向提出了见解。