泛素连接酶和去泛素化酶在阿尔茨海默病中的研究进展
Research progress of ubiquitin ligases and deubiquitinating enzymes in Alzheimer's disease
黄颖 1李雪 1高伟 1康兴宇 1李虹霖2
作者信息
- 1. 黑龙江中医药大学研究生院,哈尔滨 150040
- 2. 黑龙江中医药大学研究生院,哈尔滨 150040;黑龙江中医药大学附属第二医院,哈尔滨 150001
- 折叠
摘要
阿尔茨海默病(Alzheimer's disease,AD)是一种老年人常见的中枢神经系统退行性疾病.泛素化和去泛素化过程失调导致蛋白质异常聚集是AD发生发展的主要原因.E3泛素连接酶(E3 ubiquitin ligases,E3s)调控底物蛋白的泛素化,可促进β淀粉样蛋白(amyloid-β,Aβ)和过度磷酸化Tau蛋白的清除,改善突触及神经元的功能.去泛素化酶(deubiquitinating enzymes,DUBs)去除底物蛋白的泛素化修饰,可抑制Aβ和过度磷酸化Tau蛋白的降解,引起神经炎症.因为E3s和DUBs并不通过单一途径来促进或者抑制AD的发生发展,所以本文以E3s和DUBs所属亚族为切入点,综述了 E3s和DUBs在AD中作用机制的最新研究进展.
Abstract
Alzheimer's disease(AD)is a common degenerative disease of the central nervous system in the elderly.Abnormal process in ubiquitination and deubiquitination leading to abnormal protein aggregation is a major cause of the development of AD.E3 ubiquitin ligases(E3s)regulate the ubiquitination of substrate proteins,promote the clearance of amyloid-β and Tau proteins,and improve synaptic and neuronal functions.Deubiquitinating enzymes(DUBs)remove the ubiquitination modification of substrate proteins,inhibit the degradation of amyloid-β and Tau proteins,and cause neuroinflammation.Since E3s and DUBs do not promote or inhibit the development of AD through a single pathway,this paper reviews the latest research progress on the mechanism of E3s and DUBs in AD,using the subfamilies to which they belong as an entry point.
关键词
阿尔茨海默病/E3泛素连接酶/去泛素化酶/泛素化/去泛素化Key words
Alzheimer's disease/E3 ubiquitin ligases/deubiquitinating enzymes/ubiquitination/deubiquitination引用本文复制引用
基金项目
国家自然科学基金(82105035)
黑龙江省自然科学基金(LH2023H064)
出版年
2024
NETL
NSTL
万方数据