整合应激反应在阿尔茨海默病发病中作用的研究进展  

Research progress of integrated stress response in pathogenesis of Alzheimer's disease

作　　者：孙慧 金宏福 郭沈睿 冯奕源 尹雅芙 王辉[1] 程维维[1] SUN Hui;JIN Hongfu;GUO Shenrui;FENG Yiyuan;YIN Yafu;WANG Hui;CHENG Weiwei(Department of Nuclear Medicine/Institute of Cardiovascular Development and Regenerative Medicine,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院核医学科,心血管发育与再生医学研究所,上海200092

出　　处：《上海交通大学学报（医学版）》2023年第6期755-760,共6页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金(81901162);上海市科委基金(20QA1406300,23ZR1441200)。

摘　　要：整合应激反应是细胞受到应激刺激后产生的适应性反应,由多个磷酸激酶、磷酸酶及其他蛋白严格调控,从而维持蛋白质稳态。研究表明在阿尔茨海默病中整合应激反应被异常激活;靶向调控整合应激反应通路的不同蛋白则可抑制异常激活的整合应激反应,恢复蛋白质稳态,并缓解阿尔茨海默病模型的神经病理改变及记忆障碍。这些证据提示整合应激反应或许可成为干预阿尔茨海默病病程的新靶点。该文对整合应激反应在阿尔茨海默病中的异常激活、调控机制,以及以其为靶点在阿尔茨海默病相关模型中的研究现状进行了综述。Integrated stress response(ISR)is a cellular adaptive response induced by stress,which is strictly regulated by multiple phosphokinases,phosphatases and other proteins to maintain protein homeostasis.Studies have shown that ISR is abnormally activated in Alzheimer's disease,and targeted regulation of different proteins in ISR pathway inhibits the abnormal activation of ISR,leading to restoration of protein homeostasis and alleviation of the neuropathological changes and memory impairment in Alzheimer's disease models.These lines of evidence suggest that ISR has the potential to be a therapeutic target in Alzheimer's disease treatment.This paper reviews the abnormal activation and regulation mechanism of ISR in Alzheimer's disease and discusses the application of ISR as therapeutic targets to Alzheimer's disease models.

关 键 词：整合应激反应 阿尔茨海默病 整合应激反应抑制剂 蛋白质稳态 

分 类 号：R742[医药卫生—神经病学与精神病学]