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

作　　者：黄颖 李雪 高伟 康兴宇 李虹霖 HUANG Ying;LI Xue;GAO Wei;KANG Xing-Yu;LI Hong-Lin(Graduate School,Heilongjiang University of Chinese Medicine,Harbin 150040,China;The Second Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin 150001,China)

机构地区：[1]黑龙江中医药大学研究生院,哈尔滨150040 [2]黑龙江中医药大学附属第二医院,哈尔滨150001

出　　处：《生命科学》2024年第5期629-636,共8页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金项目(82105035);黑龙江省自然基金项目(LH2023H064)。

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。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-βand Tau proteins,and improve synaptic and neuronal functions.Deubiquitinating enzymes(DUBs)remove the ubiquitination modification of substrate proteins,inhibit the degradation of amyloid-βand 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 

分 类 号：Q512[生物学—生物化学] R749.16[医药卫生—神经病学与精神病学]