AUTHOR=Wang Yujun , Jin Yuan , Zhang Qiong , Xiong Ying , Gu Xiang , Zeng Shan , Chen Wei 

TITLE=Research progress in delineating the pathological mechanisms of GJB2-related hearing loss

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=17

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2023.1208406

DOI=10.3389/fncel.2023.1208406

ISSN=1662-5102

ABSTRACT=<p>Hearing loss is the most common congenital sensory impairment. Mutations or deficiencies of the <italic>GJB2</italic> gene are the most common genetic cause of congenital non-syndromic deafness. Pathological changes such as decreased potential in the cochlea, active cochlear amplification disorders, cochlear developmental disorders and macrophage activation have been observed in various <italic>GJB2</italic> transgenic mouse models. In the past, researchers generally believed that the pathological mechanisms underlying <italic>GJB2</italic>-related hearing loss comprised a K<sup>+</sup> circulation defect and abnormal ATP-Ca<sup>2+</sup> signals. However, recent studies have shown that K<sup>+</sup> circulation is rarely associated with the pathological process of <italic>GJB2</italic>-related hearing loss, while cochlear developmental disorders and oxidative stress play an important, even critical, role in the occurrence of <italic>GJB2</italic>-related hearing loss. Nevertheless, these research has not been systematically summarized. In this review, we summarize the pathological mechanisms of <italic>GJB2</italic>-related hearing loss, including aspects of K<sup>+</sup> circulation, developmental disorders of the organ of Corti, nutrition delivery, oxidative stress and ATP-Ca<sup>2+</sup> signals. Clarifying the pathological mechanism of <italic>GJB2</italic>-related hearing loss can help develop new prevention and treatment strategies.</p>