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Sirtuin2(SIRT2)是一种烟酰胺腺嘌呤二核苷酸(NAD~+)依赖性的组蛋白去乙酰化酶,是沉默信息调节因子2(Sir2)相关蛋白家族的重要成员。SIRT2通过催化不同的底物去乙酰化参与了许多生物学过程,比如基因沉默、细胞周期调控、细胞代谢、细胞凋亡等。研究表明,在许多神经退行性疾病模型中,抑制SIRT2能够对神经元细胞产生明显的保护作用。因此,SIRT2有望成为治疗神经退行性疾病的重要靶点。本文主要对SIRT2的结构、功能、SIRT2与神经退行性疾病的关系、SIRT2抑制剂及其构效关系做一综述,旨在为以SIRT2为靶点的神经退行性疾病药物研发提供参考。
Sirtuin2 (SIRT2) is a niacinamide adenine dinucleotide (NAD ~ +) -dependent histone deacetylase that is an important member of the sfr2-related protein family. SIRT2 is involved in many biological processes such as gene silencing, cell cycle regulation, cell metabolism, apoptosis, etc. by deacetylating different substrates. Studies have shown that in many neurodegenerative disease models, inhibition of SIRT2 can have a significant protective effect on neuronal cells. Therefore, SIRT2 is expected to be an important target for the treatment of neurodegenerative diseases. This review summarizes the structure and function of SIRT2, the relationship between SIRT2 and neurodegenerative diseases, and the SIRT2 inhibitors and their structure-activity relationships. This review aims to provide a reference for the development of SIRT2-targeted neurodegenerative diseases.