The α9α10 nicotinic acetylcholine receptor: a compelling drug target for hearing loss?

Abstract

Introduction: Hearing loss is a major health problem, impacting education, communication, interpersonal relationships, and mental health. Drugs that prevent or restore hearing are lacking and hence novel drug targets are sought. There is the possibility of targeting the α9α10 nicotinic acetylcholine receptor (nAChR) in the prevention of noise-induced, hidden hearing loss and presbycusis. This receptor mediates synaptic transmission between medial olivocochlear efferent fibers and cochlear outer hair cells. This target is key since enhanced olivocochlear activity prevents noise-induced hearing loss and delays presbycusis. Areas covered: The work examines the α9α10 nicotinic acetylcholine receptor (nAChR), its role in noiseinduced, hidden hearing loss and presbycusis and the possibility of targeting. Data has been searched in Pubmed, the World Report on Hearing from the World Health Organization and the Global Burden of Disease Study 2019. Expert opinion: The design of positive allosteric modulators of α9α10 nAChRs is proposed because of the advantage of reinforcing the medial olivocochlear (MOC)-hair cell endogenous neurotransmission without directly stimulating the target receptors, therefore avoiding receptor desensitization and reduced efficacy. The time is right for the discovery and development of α9α10 nAChRs targeting agents and high throughput screening assays will support this.