去乙酰化酶SIRT2及其抑制剂的研究进展

Recent advances on deacetylase SIRT2 and its inhibitors

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。

Sirtuin 2（ SIRT2）,an important member of sirtuins family,is a kind of nicotinamide adenine dinucleotide（ NAD^＋）-dependent deacetylase. SIRT2 is involved in several of biological process,such as gene silencing,cell-cycle regulation,metabolism,apoptosis,through deacetylating various substrates. It has been demonstrated that SIRT2 inhibition is protective for neurons in models of neurodegenerative disease. Thus,SIRT2 is expected to be an important target for neurodegenerative disease prevention. In this review,the structure and biological function of SIRT2,the relationships betw een SIRT2 and neurodegenerative disease,the structure-activity relationships of diverse structural inhibitors for SIRT2 w ere summarized to provide a guideline for further research of SIRT2 inhibitors for neurodegenerative disease treatment.