Jacobs Journal of Molecular and Translational Medicine

TLR Signaling Pathway Regulation in Association with Autophagy in the Diseased Inner Ear

*Jing Zou
Department Of Otolaryngology Head And Neck Surgery, Second Military Medical University, China

*Corresponding Author:
Jing Zou
Department Of Otolaryngology Head And Neck Surgery, Second Military Medical University, China
Email:zoujinghb@hotmail.com

Published on: 2018-09-15

Abstract

Inner ear diseases, such as Meniere’s disease and sensorineural hearing loss, significantly impact the work capacity and life quality of affected patients because of the lack of efficient treatments. The causes and mechanisms underlying Meniere’s disease and idiopathic sensorineural hearing loss remain unknown. Inflammation secondary to infection or insufficiency of blood supply are accepted as critical steps toward inner ear impairment. Advancements in the understanding of inflammatory signaling pathways have provided an avenue to discover the molecular mechanisms underlying inner ear disease. The present review summarizes advances in knowledge of pattern recognition receptor (PRR) pathway activation, especially with respect to Toll-like receptor (TLR), which plays an important role in the pathological process of inner ear disease. Hyaluronic acid (HYA) is an important molecule in the inner ear and accumulates in the pathological inner ear. HYA receptors are up regulated in the inner ear under pathological conditions. As the most deleterious regulatory mechanism of the TLR signaling pathway, autophagy is beneficial for the cochlea by suppressing potential excess inflammatory reactions via the degradation of key proteins such as A20 and nuclear dot protein-52.

Keywords

Hearing Loss; Vertigo; Receptor ; Inflammation;Immune Reaction; Autophagy.

Introduction

Inner ear diseases, such as Meniere’s disease and sensorineural hearing loss, significantly impact the work capacity and life quality of affected patients because of the lack of efficient treatments. In China, the overall prevalence of hearing disability is 2.11% [1]. It has been estimated that hearing loss in the USA causes annually costs of 144 billion$ [2]. Balance problems, dizziness and vertigo form another symptom entity related to falls that interferes with quality of life and especially in the elderly drives the individual participants to enter controlled care units in residential homes. In 2011 the total extrapolated costs caused by vertigo and dizziness at emergency department in the USA has been estimated to be $3.9 billion and from that the otologic/vestibular causes were 25.7% ($768; $757 million) [3]. The etiology of Meniere’s disease and idiopathic sensorineural hearing loss is unknown. Viral infection, metabolic disorder, immune reaction, inflammation, impaired quality of sleep, and stress are reportedly involved in the occurrence of Meniere’s disease and idiopathic sensorineural hearing loss [4-10]. However, the mechanisms underlying inner ear diseases have not yet been elucidated. Meniere’s disease and idiopathic monosymptomatic auditory diseases, such as sudden deafness and other sensorineural hearing loss may have similar mechanism [5]. The delayed endolymphatic hydrops is a good example of linking the pathogenesis of Meniere’s disease and other sensorineural hearing loss [11]. A study of mining immune epitopes in the inner ear identified 3036 and 106 unique epitope matches, respectively, the majority of which were infectious epitopes [12]. This suggests that infection-associated reaction may play an important role in the inner ear diseases.