G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss

Xiangyu Ma; Jiamin Guo; Yaoyang Fu; Cangsong Shen; Pei Jiang; Yuan Zhang; Lei Zhang; Yafeng Yu; Jiangang Fan; Renjie Chai

doi:10.3389/fnmol.2022.1028125

G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss

Front Mol Neurosci. 2022 Oct 12:15:1028125. doi: 10.3389/fnmol.2022.1028125. eCollection 2022.

Authors

Xiangyu Ma¹, Jiamin Guo¹, Yaoyang Fu², Cangsong Shen³, Pei Jiang¹, Yuan Zhang^{4

5}, Lei Zhang⁶, Yafeng Yu⁷, Jiangang Fan⁸, Renjie Chai^{1

8

9

10

11}

Affiliations

¹ State Key Laboratory of Bioelectronics, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
² Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
⁴ Jiangsu Provincial Key Medical Discipline (Laboratory), Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
⁵ Research Institute of Otolaryngology, Nanjing, China.
⁶ Department of Otorhinolaryngology, Head and Neck Surgery, The Second Hospital of Anhui Medical University, Hefei, China.
⁷ First Affiliated Hospital of Soochow University, Soochow, China.
⁸ Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
⁹ Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
¹⁰ Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
¹¹ Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China.

Abstract

The prevalence of hearing loss-related diseases caused by different factors is increasing worldwide year by year. Currently, however, the patient's hearing loss has not been effectively improved. Therefore, there is an urgent need to adopt new treatment measures and treatment techniques to help improve the therapeutic effect of hearing loss. G protein-coupled receptors (GPCRs), as crucial cell surface receptors, can widely participate in different physiological and pathological processes, particularly play an essential role in many disease occurrences and be served as promising therapeutic targets. However, no specific drugs on the market have been found to target the GPCRs of the cochlea. Interestingly, many recent studies have demonstrated that GPCRs can participate in various pathogenic process related to hearing loss in the cochlea including heredity, noise, ototoxic drugs, cochlear structure, and so on. In this review, we comprehensively summarize the functions of 53 GPCRs known in the cochlea and their relationships with hearing loss, and highlight the recent advances of new techniques used in cochlear study including cryo-EM, AI, GPCR drug screening, gene therapy vectors, and CRISPR editing technology, as well as discuss in depth the future direction of novel GPCR-based drug development and gene therapy for cochlear hearing loss. Collectively, this review is to facilitate basic and (pre-) clinical research in this area, and provide beneficial help for emerging GPCR-based cochlear therapies.

Keywords: G protein-coupled receptors; cochlea; drug therapy; gene therapy; hearing loss.

Publication types

Review