Wu Jichang, Ji Peilin, Zhang Andi, Hu Haixia, Shen Yilin, Wang Quan, Fan Cui, Chen Kaili, Ding Rui, Huang Weiyi, Xiang Mingliang, Ye Bin
Department of Otolaryngology and Head and Neck Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Audiology and Speech-Language Pathology, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Cell Neurosci. 2024 Jan 4;17:1308028. doi: 10.3389/fncel.2023.1308028. eCollection 2023.
Cholesterol is the most abundant sterol molecule in mammalian cells, which not only constitutes the cell membrane but also plays essential roles in the synthesis of important hormones, synapse formation, and cell signal transduction. The effect of hypercholesterolemia on hearing has been studied extensively, and multiple studies have demonstrated that hypercholesterolemia is a risk factor for hearing loss. However, the impact of cholesterol homeostasis within auditory cells on peripheral auditory development and maintenance has not been evaluated in detail. Mutations in certain cholesterol metabolism-related genes, such as , , , and , as well as derivatives of cholesterol metabolism-related ototoxic drugs, such as β-cyclodextrin, can lead to disruptions of cholesterol homeostasis within auditory cells, resulting in hearing loss. This article aims to review the impact of cholesterol homeostasis within auditory cells on the peripheral auditory function from the following two perspectives: (1) changes in cholesterol homeostasis regulatory genes in various hearing loss models; (2) mechanisms underlying the effects of some drugs that have a therapeutic effect on hearing loss via regulating cholesterol homeostasis. This article aims to summarize and analyze the impact of disruption of cellular cholesterol homeostasis within auditory cells on hearing, in order to provide evidence regarding the underlying mechanisms.
胆固醇是哺乳动物细胞中含量最丰富的固醇分子，它不仅构成细胞膜，还在重要激素的合成、突触形成和细胞信号转导中发挥关键作用。高胆固醇血症对听力的影响已得到广泛研究，多项研究表明高胆固醇血症是听力损失的一个危险因素。然而，听觉细胞内胆固醇稳态对周围听觉发育和维持的影响尚未得到详细评估。某些与胆固醇代谢相关的基因突变，如[此处原文缺失具体基因名称]，以及胆固醇代谢相关耳毒性药物的衍生物，如β-环糊精，可导致听觉细胞内胆固醇稳态的破坏，从而导致听力损失。本文旨在从以下两个角度综述听觉细胞内胆固醇稳态对周围听觉功能的影响：（1）各种听力损失模型中胆固醇稳态调节基因的变化；（2）一些通过调节胆固醇稳态对听力损失有治疗作用的药物的作用机制。本文旨在总结和分析听觉细胞内细胞胆固醇稳态破坏对听力的影响，以便为潜在机制提供证据。
