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中华脑科疾病与康复杂志(电子版) ›› 2025, Vol. 15 ›› Issue (05) : 298 -302. doi: 10.3877/cma.j.issn.2095-123X.2025.05.008

综述

PERK在神经退行性变性疾病中作用机制的研究进展
徐弢, 张丽蓉, 连红强()   
  1. 730050 兰州,甘肃省中医院康复医学科
  • 收稿日期:2024-12-17 出版日期:2025-10-15
  • 通信作者: 连红强

Progress on the mechanism of PERK in neurodegene-rative diseases

Tao Xu, Lirong Zhang, Hongqiang Lian()   

  1. Department of Rehabilitation Medicine, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China
  • Received:2024-12-17 Published:2025-10-15
  • Corresponding author: Hongqiang Lian
  • Supported by:
    Gansu Provincial Administration of Traditional Chinese Medicine Project(GZK-2019-4); Lanzhou Talent Innovation and Entrepreneurship Project(2018-RC-94)
引用本文:

徐弢, 张丽蓉, 连红强. PERK在神经退行性变性疾病中作用机制的研究进展[J/OL]. 中华脑科疾病与康复杂志(电子版), 2025, 15(05): 298-302.

Tao Xu, Lirong Zhang, Hongqiang Lian. Progress on the mechanism of PERK in neurodegene-rative diseases[J/OL]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2025, 15(05): 298-302.

蛋白激酶R样内质网激酶(PERK)可调节真核细胞启动因子2信号转导级联失活,以应对细胞压力。细胞和内质网(ER)应激会激活未折叠蛋白反应(UPR)信号通路,ER功能受到抑制引发蛋白质折叠和聚集异常,导致突触和神经元功能障碍。蛋白质异常聚集诱发ER应激状态促使UPR转向凋亡,引发神经退行性变。线粒体膜与ER膜相连,ER应激激活PERK调控线粒体动态适应,PERK激活引起线粒体融合,还可增加线粒体嵴的生成和呼吸链复合物的形成。线粒体损伤和氧化应激与阿尔茨海默病、帕金森病、亨廷顿病和多发性硬化等神经退行性变性疾病的发病机制密切相关。本文综述了PERK与神经退行性变性疾病的相关机制,旨在为神经退行性变性疾病的治疗提供相关理论依据。

Protein kinase R-like endoplasmic reticulum kinase (PERK) can regulate the inactivation of the eukaryotic initiation factor 2 signalling cascade in response to cellular stress. Cellular and endoplasmic reticulum (ER) stress activates the unfolded protein response (UPR) signalling pathway, and ER dysfunction leads to abnormal protein folding and aggregation, causing synaptic and neuronal dysfunction. Abnormal protein aggregation induces an ER stress state, promoting the UPR to shift towards apoptosis, resulting in neurodegeneration. The mitochondrial membrane is connected to the ER membrane, and ER stress activates PERK to regulate mitochondrial dynamics adaptation; PERK activation induces mitochondrial fusion; PERK activation increases the formation of mitochondrial cristae and respiratory chain complexes. Mitochondrial damage and oxidative stress are closely related to the pathogenesis of neurodegene-rative diseases such as Alzheimer disease, Parkinson disease, Huntington disease, and multiple sclerosis. This article reviews the mechanisms of PERK in neurodegene-rative diseases, aiming to provide theoretical basis for the treatment of neurodegene-rative diseases.

图1 ER应激激活PERK引起神经病变的机制ER:内质网;PERK:蛋白激酶R样内质网激酶;eIF2α:真核细胞启动因子2α;ATF4:转录激活因子4;CHOP:增强子结合蛋白同源蛋白;ROS:活性氧
Fig.1 Mechanism of PERK-induced neuropathy by activation of PERK by ER stress
图2 PERK与神经退行性变性疾病的作用机制PERK:蛋白激酶R样内质网激酶;eIF2:真核细胞启动因子2;Nrf2:细胞核因子E2相关因子2;ATF4:转录激活因子4;Htt:亨廷顿蛋白;CHOP:增强子结合蛋白同源蛋白
Fig.2 Mechanism of PERK in neurodegene-rative diseases
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