Li Guanzhen, Yang Huiming, Zhang Peiyuan, Guo Yan, Yuan Lili, Xu Shujiao, Yuan Yingxue, Xiong Huabao, Yin Haiyan
School of Clinical Medicine, Jining Medical University, Jining, Shandong, China.
Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Front Mol Neurosci. 2024 Dec 18;17:1443401. doi: 10.3389/fnmol.2024.1443401. eCollection 2024.
Sensorineural hearing loss (SNHL) is characterized by a compromised cochlear perception of sound waves. Major risk factors for SNHL include genetic mutations, exposure to noise, ototoxic medications, and the aging process. Previous research has demonstrated that inflammation, oxidative stress, apoptosis, and autophagy, which are detrimental to inner ear cells, contribute to the pathogenesis of SNHL; however, the precise mechanisms remain inadequately understood. The endoplasmic reticulum (ER) plays a key role in various cellular processes, including protein synthesis, folding, lipid synthesis, cellular calcium and redox homeostasis, and its homeostatic balance is essential to maintain normal cellular function. Accumulation of unfolded or misfolded proteins in the ER leads to endoplasmic reticulum stress (ERS) and activates the unfolded protein response (UPR) signaling pathway. The adaptive UPR has the potential to reestablish protein homeostasis, whereas the maladaptive UPR, associated with inflammation, oxidative stress, apoptosis, and autophagy, can lead to cellular damage and death. Recent evidence increasingly supports the notion that ERS-mediated cellular damage responses play a crucial role in the initiation and progression of various SNHLs. This article reviews the research advancements on ERS in SNHL, with the aim of elucidating molecular biological mechanisms underlying ERS in SNHL and providing novel insights for the treatment.
感音神经性听力损失（SNHL）的特征是耳蜗对声波的感知受损。SNHL的主要危险因素包括基因突变、接触噪音、耳毒性药物和衰老过程。先前的研究表明，对内耳细胞有害的炎症、氧化应激、细胞凋亡和自噬促成了SNHL的发病机制；然而，确切机制仍未得到充分理解。内质网（ER）在包括蛋白质合成、折叠、脂质合成、细胞钙和氧化还原稳态在内的各种细胞过程中起关键作用，其稳态平衡对于维持正常细胞功能至关重要。内质网中未折叠或错误折叠蛋白质的积累会导致内质网应激（ERS）并激活未折叠蛋白反应（UPR）信号通路。适应性UPR有重新建立蛋白质稳态的潜力，而与炎症、氧化应激、细胞凋亡和自噬相关的适应性不良的UPR会导致细胞损伤和死亡。最近的证据越来越支持这样一种观点，即ERS介导的细胞损伤反应在各种SNHL的发生和发展中起关键作用。本文综述了SNHL中ERS的研究进展，旨在阐明SNHL中ERS的分子生物学机制并为治疗提供新的见解。
