Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss
Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea
Department of Otorhinolaryngology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea
Authors to whom correspondence should be addressed.
Academic Editor: Srdjan M Vlajkovic
Int. J. Mol. Sci. 2021, 22(5), 2510; https://doi.org/10.3390/ijms22052510
Received: 20 January 2021 / Revised: 16 February 2021 / Accepted: 22 February 2021 / Published: 2 March 2021
(This article belongs to the Special Issue Molecular Mechanisms of Sensorineural Hearing Loss and Development of Inner Ear Therapeutics)
Potassium voltage-gated channel subfamily q member 4 (KCNQ4) is a voltage-gated potassium channel that plays essential roles in maintaining ion homeostasis and regulating hair cell membrane potential. Reduction of the activity of the KCNQ4 channel owing to genetic mutations is responsible for nonsyndromic hearing loss, a typically late-onset, initially high-frequency loss progressing over time. In addition, variants of KCNQ4 have also been associated with noise-induced hearing loss and age-related hearing loss. Therefore, the discovery of small compounds activating or potentiating KCNQ4 is an important strategy for the curative treatment of hearing loss. In this review, we updated the current concept of the physiological role of KCNQ4 in the inner ear and the pathologic mechanism underlying the role of KCNQ4 variants with regard to hearing loss. Finally, we focused on currently developed KCNQ4 activators and their pros and cons, paving the way for the future development of specific KCNQ4 activators as a remedy for hearing loss.