中国全科医学2025,Vol.28Issue(9) :1143-1155.DOI:10.12114/j.issn.1007-9572.2024.0357

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

徐林慧 李鹏飞 吴苗苗 康丽华 季敏 俞莹 管怀进
中国全科医学2025,Vol.28Issue(9) :1143-1155.DOI:10.12114/j.issn.1007-9572.2024.0357

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

徐林慧 1李鹏飞 1吴苗苗 1康丽华 1季敏 1俞莹 1管怀进1
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作者信息

  • 1. 226001 江苏省南通市,南通大学;226001 江苏省南通市,南通大学附属医院眼科研究所
  • 折叠

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.

Abstract

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

Key words

Aging/Age-related diseases/Deubiquitination/Deubiquitinating enzymes/Protein quality control/Mitochondrial function

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出版年

2025
中国全科医学
中国医院协会

中国全科医学

北大核心
影响因子:2.04
ISSN:1007-9572
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