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未折叠蛋白应答通路调控机制的研究进展及其临床应用前景
郭筱华赵忠新
0
(第二军医大学长征医院神经内科,上海200003)
摘要:
未折叠蛋白应答(unfolded protein response,UPR)是应激条件下细胞中内质网的一种保护性反应。在哺乳动物中,其主要通过内质网跨膜蛋白(IRE1、PERK及ATF6)转导的3条信号通路发挥效应,并依赖相关蛋白、因子进行正负反馈调控,以维持细胞功能正常。如果应激持续存在,UPR调控失衡,诱导细胞凋亡或死亡,引发相关疾病。不少研究选取UPR通路中的关键因子作为疾病治疗靶点,取得一些进展,提供了新的临床思路,具有广阔的应用前景。[
关键词:  内质网 蛋白质折叠 基因表达调控 细胞凋亡
DOI:10.3724/SP.J.1008.2007.00325
基金项目:
Regulation mechanism of unfolded protein response: progress and clinical prospect
GUO Xiao-hua, ZHAO Zhong-xin
(Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China)
Abstract:
Unfolded protein response(UPR) is a protective response in cell endoplasmic reticulum (ER) under stress condition. Three ER transmembrane proteins, IRE1, PERK, and ATF6, coordinately regulate the UPR function in mammalian cells through their signaling pathways. In addition, some proteins and transcription factors during the UPR can provide negative and positive feedback loops to maintain the normal function of ER. UPR can trigger cell death or apoptosis and eventually cause related diseases if the ER stress persists. Several key mediators of UPR are candidates for therapeutic targets in many studies. Up to now progress has been made in the area, which provides new ideas for clinical practice and holds a great potential for future application.[
Key words:  endoplasmic reticulum  protein folding  gene expression regulation  apoptosis