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内质网质量控制系统：椎间盘退变治疗的潜在靶点

孙钰¹, 刘恩旭¹, 李兆勇¹, 段嘉豪¹, 孙飞¹, 杨雷², 杨少锋^2,*

¹湖南中医药大学研究生院，长沙 410208；²湖南中医药大学第一附属医院骨科，长沙 410208

摘要

内质网(endoplasmic reticulum, ER)作为真核细胞中最大的细胞器，调控细胞内蛋白质折叠、翻译与组装等过程。在ER中存在的多种质量控制机制确保ER腔内蛋白质被准确修饰，并在维持机体钙稳态、氧化应激、细胞衰老和凋亡等方面发挥重要作用。这些机制主要包括ER应激(ER stress, ERS)、ER自噬(ER-phagy, ERPA)与ER相关降解(ER-associated degradation, ERAD)。椎间盘退变(intervertebral disc degeneration, IDD)是一种与年龄相关的脊柱退行性疾病。尽管其发病机制尚未完全阐明，但已有研究发现ER质量控制系统可能参与IDD演变。此外，先前大多研究主要集中于线粒体质量控制及其介导疾病演变的相关机制，罕有文献针对ER质量控制系统进行系统总结。基于此，本文全面综述了ER质量控制系统的分子生物学机制，并探讨了ER质量控制系统与IDD的关联。同时，我们还总结了目前靶向ER质量控制系统延缓IDD进展的潜在治疗途径，为IDD的病理发生机制及再生修复策略提供了新视角。

关键词： 内质网自噬; 内质网相关降解; 内质网应激; 椎间盘退变

Endoplasmic reticulum quality control system: a potential target for the treatment of intervertebral disc degeneration

SUN Yu¹, LIU En-Xu¹, LI Zhao-Yong¹, DUAN Jia-Hao¹, SUN Fei¹, YANG Lei², YANG Shao-Feng^2,*

¹Graduate School of Hunan University of Chinese Medicine, Changsha 410208, China；²Department of Orthopedics, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410208, China

Abstract

As the largest organelle in eukaryotic cells, the endoplasmic reticulum (ER) plays a crucial role in regulating intracellular protein folding, translation and assembly. Multiple quality control mechanisms in the ER ensure accurate modification of proteins in the ER lumen are accurately modified, thus maintaining calcium homeostasis, oxidative stress, cellular senescence and apoptosis. These mechanisms include ER stress (ERS), ER autophagy (ER-phagy, ERPA) and ER-associated degradation (ERAD). Intervertebral disc degeneration (IDD) is an age-related degenerative disease of the spine. Although the pathogenesis of IDD has not been fully elucidated, emerging evidence suggests that the ER quality control system may be involved in its progression. Previous studies have focused on mitochondrial quality control and its related mechanisms in diseases, with limited systematic summaries on the ER quality control system. In this paper, we comprehensively reviewed the molecular mechanisms of the ER quality control system and investigated its association with IDD. In addition, we summarized the potential therapeutic strategies targeting the ER quality control system to attenuate IDD progression, offering new insights into the pathogenesis and regenerative repair strategies of IDD.

Key words: endoplasmic reticulum autophagy; endoplasmic reticulum-associated degradation; endoplasmic reticulum stress; intervertebral disc degeneration

收稿日期：　　录用日期：

通讯作者：杨少锋　　E-mail:

DOI: 10.13294/j.aps.2024.0033

引用本文：

孙钰, 刘恩旭, 李兆勇, 段嘉豪, 孙飞, 杨雷, 杨少锋. 内质网质量控制系统：椎间盘退变治疗的潜在靶点[J]. 生理学报 2024; 76 (4): 561-575.

SUN Yu, LIU En-Xu, LI Zhao-Yong, DUAN Jia-Hao, SUN Fei, YANG Lei, YANG Shao-Feng. Endoplasmic reticulum quality control system: a potential target for the treatment of intervertebral disc degeneration. Acta Physiol Sin 2024; 76 (4): 561-575 (in Chinese with English abstract).