Key Signaling Pathways Regulate the Development and Survival of Auditory Hair Cells.

Yao Liu,Peng Lin,Wei Wang,Mei Wei,Taisheng Chen,Xiang Mao,Daniela Tropea

doi:10.1155/2021/5522717

Abstract

The loss of auditory sensory hair cells (HCs) is the most common cause of sensorineural hearing loss (SNHL). As the main sound transmission structure in the cochlea, it is necessary to maintain the normal shape and survival of HCs. In this review, we described and summarized the signaling pathways that regulate the development and survival of auditory HCs in SNHL. The role of the mitogen-activated protein kinase (MAPK), phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), Notch/Wnt/Atoh1, calcium channels, and oxidative stress/reactive oxygen species (ROS) signaling pathways are the most relevant. The molecular interactions of these signaling pathways play an important role in the survival of HCs, which may provide a theoretical basis and possible therapeutic interventions for the treatment of hearing loss.

Highlights

Hearing loss is the most common sensory disorder, and its severity ranges from mild hearing impairment to total deafness
Hearing loss can be divided into three types according to the location of the lesion: conductive hearing loss (CHL), sensorineural hearing loss (SNHL), and mixed hearing loss
P38 is another downstream protein of the mitogen-activated protein kinase (MAPK) pathway and is involved in many cellular processes, including inflammation, cell cycle regulation, and apoptosis [48]

Summary

Introduction

Hearing loss is the most common sensory disorder, and its severity ranges from mild hearing impairment to total deafness. Various causes of hearing loss have been identified and studied, such as aging, ototoxic drugs, genetic mutations of deafness genes, ear or brain tumors, and exposure to loud noises (even for short time) [2, 3]. These causes determine the specific type of hearing loss and the treatment orientation. There are an increasing number of studies that have focused on cellular molecular pathways that could represent potential checkpoints in the mechanism of hearing loss and HC damage. The potential of damage and survival mechanisms as targets for pharmacological intervention to prevent or ameliorate hearing loss is reviewed, and conclusions are drawn in the last section

MAPK Signaling

Calcium Channel

Oxidative Stress and ROS Signaling

Conclusion