去泛素化修饰在衰老相关疾病中的研究进展  

The Roles of Deubiquitination in Age-related Diseases

作　　者：徐林慧 李鹏飞 吴苗苗 康丽华 季敏[1,2] 俞莹 管怀进[1,2] XU Linhui;LI Pengfei;WU Miaomiao;KANG Lihua;JI Min;YU Ying;GUAN Huaijin(Nantong University,Nantong 226001,China;Eye Institute,Affiliated Hospital of Nantong University,Nantong 226001,China)

机构地区：[1]南通大学,江苏省南通市226001 [2]南通大学附属医院眼科研究所,江苏省南通市226001

出　　处：《中国全科医学》2025年第9期1143-1155,共13页Chinese General Practice

基　　金：国家自然科学基金资助项目(81974129,82171038);江苏省医学重点学科(JSDW202245)。

摘　　要：去泛素化修饰是由去泛素化酶(DUBs)介导的一类重要的蛋白质翻译后修饰,其主要机制是DUBs与泛素化靶蛋白相互作用,切割或去除靶蛋白的泛素链,进而恢复蛋白的表达水平和功能活性。本文系统性地综述了去泛素化修饰在衰老相关疾病中的最新研究进展,涵盖了DUBs的种类、DUBs在细胞衰老中的作用,以及不同机制对衰老相关疾病的调控,并总结了针对DUBs小分子药物开发以及相关机制的研究进展。本文表明,随着机体的衰老,蛋白更新功能减慢、氧化损伤等因素导致泛素化蛋白累积等,进而细胞出现功能障碍。DUBs通过调节衰老细胞的蛋白质稳态、线粒体功能、细胞周期等机制,在衰老相关疾病中发挥重要且复杂的调控作用。Deubiquitination,mediated by deubiquitinating enzymes(DUBs),represents a crucial class of post-translational protein modifications.Its primary mechanism involves in the interaction of DUBs with ubiquitinated target proteins,whereby the DUBs cleave or remove ubiquitin chains from these targets,subsequently restoring their expression levels and functional activities.This article systematically reviews the latest research progress on deubiquitination in age-related diseases,covering the types of DUBs,their roles in cellular aging,and the regulatory mechanisms in age-related diseases through different pathways.It also summarizes the research progress in the development of small-molecule drugs targeting DUBs and related mechanisms.This review demonstrates that as the body ages,factors such as decreased protein renewal function and oxidative damage lead to the accumulation of ubiquitinated proteins,resulting in cellular dysfunction.DUBs play an important and complex regulatory role in age-related diseases by modulating mechanisms such as protein homeostasis,mitochondrial function,and cell cycle in aging cells.

关 键 词：衰老 衰老相关疾病 去泛素化修饰 去泛素酶类 蛋白质质量控制 线粒体功能 

分 类 号：R33[医药卫生—人体生理学] R349.1[医药卫生—基础医学]