《生命科学》 2024, 36(5): 629-636

泛素连接酶和去泛素化酶在阿尔茨海默病中的研究进展

黄　颖¹ , 李　雪¹ , 高　伟¹ , 康兴宇¹ , 李虹霖^1,2,*

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

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。

通讯作者：李虹霖 , Email:flyada001@163.com

Research progress of ubiquitin ligases and deubiquitinating enzymes in Alzheimer's disease

HUANG Ying¹ , LI Xue¹ , GAO Wei¹ , KANG Xing-Yu¹ , LI Hong-Lin^1,2,*

¹Graduate School, Heilongjiang University of Chinese Medicine, Harbin 150040, China ²The Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150001, China

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.

Communication Author：LI Hong-Lin , Email:flyada001@163.com