Impact of cholesterol homeostasis within cochlear cells on auditory development and hearing loss

Jichang Wu; Peilin Ji; Andi Zhang; Haixia Hu; Yilin Shen; Quan Wang; Cui Fan; Kaili Chen; Rui Ding; Weiyi Huang; Mingliang Xiang; Bin Ye

doi:10.3389/fncel.2023.1308028

Impact of cholesterol homeostasis within cochlear cells on auditory development and hearing loss

Front Cell Neurosci. 2024 Jan 4:17:1308028. doi: 10.3389/fncel.2023.1308028. eCollection 2023.

Authors

Jichang Wu^#¹, Peilin Ji^#¹, Andi Zhang^#¹, Haixia Hu¹, Yilin Shen¹, Quan Wang¹, Cui Fan¹, Kaili Chen¹, Rui Ding¹, Weiyi Huang¹, Mingliang Xiang^#^{1

2}, Bin Ye^#¹

Affiliations

¹ Department of Otolaryngology and Head and Neck Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Audiology and Speech-Language Pathology, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

^# Contributed equally.

Abstract

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 NPC1, SERAC1, DHCR7, and OSBPL2, 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.

Keywords: cholesterol homeostasis; cochlea; hearing loss; hypercholesterolemia; therapeutic targets.

Publication types

Review

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the National Natural Science Foundation of China (grant Nos. 82101212, 82101209, 82301296, and 82301297), Science and Technology Commission of Shanghai Municipality (grant Nos. 23ZR1440200, 21ZR1440200, and SHDC2020CR1044B-003), and Shanghai “Rising Stars of Medical Talents” Youth Development Program and Shanghai Municipal Hospital ENT Specialist Alliance.