泛素连接酶和去泛素化酶在阿尔茨海默病中的作用研究  

Ubiquitin ligase and deubiquitin enzyme in Alzheimer’s disease function study

作　　者：王语晴 侯志涛[1] 李松哲 郝志华 陈晶[1] WANG Yu-qing;HOU Zhi-tao;LI Song-zhe;HAO Zhi-hua;CHEN Jing(School of Basic Medicine,Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学基础医学院,黑龙江哈尔滨150040

出　　处：《中国药理学通报》2025年第3期427-433,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82274395);黑龙江省自然科学基金项目(No YQ2022H019)。

摘　　要：阿尔茨海默病(Alzheimer’s disease,AD)是一种以有毒蛋白质聚集和相关神经变性为特征的多因素疾病。AD以β-淀粉样蛋白(amyloid beta,Aβ)和Tau蛋白的病理性沉积为特征,Aβ和Tau蛋白之间的相互作用能够进一步诱导神经炎症、线粒体自噬障碍和内质网应激,加剧突触损伤及神经元死亡。神经元细胞对蛋白质错误折叠特别敏感,引起这些病理特征的原因之一可能是相关蛋白生成与降解的失衡。泛素/26S蛋白酶体系统(ubiquitin/26S proteasome system,UPS)能够识别神经系统中错误折叠或损伤的蛋白质,是真核细胞内蛋白质降解的主要途径之一。在UPS中,泛素化水平受到泛素连接酶(ubiquitin ligases,E3s)和去泛素化酶(deubiquitylases,DUBs)共同严格调控。该文综述了E3s和DUBs酶在AD发生发展中的作用及其机制,以期为AD的治疗提供新的研究策略。Alzheimer’s disease(AD)is a multifactorial condition characterized by the accumulation of toxic proteins and associated neurodegeneration.AD is distinguished by the pathological aggregation of amyloid beta(Aβ)and Tau proteins.The interaction between Aβand Tau can further induce neuroinflammation,mitochondrial autophagy dysfunction,and endoplasmic reticulum stress,exacerbating synaptic damage and neuronal death.Neuronal cells are particularly susceptible to protein misfolding due to an imbalance between protein production and degradation.The ubiquitin/26S proteasome system(UPS),a major pathway for protein degradation in eukaryotic cells,plays a crucial role in recognizing misfolded or damaged proteins within the nervous system.In UPS,the levels of ubiquitin are tightly regulated by both ubiquitin ligases(E3s)and deubiquitylases(DUBs).This article reviews the involvement and mechanisms of E3s and DUBs in the pathogenesis of AD,aiming to provide novel research strategies for its treatment.

关 键 词：阿尔茨海默病 Β-淀粉样蛋白 TAU蛋白 泛素化 泛素连接酶 去泛素化酶 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R341[医药卫生—基础医学] R745.7R977.3R977.6