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内质网质量控制系统:治疗椎间盘退变的潜在靶点

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

作者信息

Sun Yu, Liu En-Xu, Li Zhao-Yong, Duan Jia-Hao, Sun Fei, Yang Lei, Yang Shao-Feng

机构信息

Graduate School of Hunan University of Chinese Medicine, Changsha 410208, China.

Department of Orthopedics, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410208, China.

出版信息

Sheng Li Xue Bao. 2024 Aug 25;76(4):561-575.

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.

摘要

作为真核细胞中最大的细胞器,内质网(ER)在调节细胞内蛋白质折叠、翻译和组装方面发挥着关键作用。内质网中的多种质量控制机制确保内质网腔中的蛋白质得到准确修饰,从而维持钙稳态、氧化应激、细胞衰老和凋亡。这些机制包括内质网应激(ERS)、内质网自噬(ER自噬,ERPA)和内质网相关降解(ERAD)。椎间盘退变(IDD)是一种与年龄相关的脊柱退行性疾病。尽管IDD的发病机制尚未完全阐明,但新出现的证据表明内质网质量控制系统可能参与其进展。以往的研究主要集中在线粒体质量控制及其在疾病中的相关机制,对内质网质量控制系统的系统性总结有限。在本文中,我们全面综述了内质网质量控制系统的分子机制,并研究了其与IDD的关联。此外,我们总结了针对内质网质量控制系统以减轻IDD进展的潜在治疗策略,为IDD的发病机制和再生修复策略提供了新的见解。

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