ER Stress Inhibitor Attenuates Hearing Loss and Hair Cell Death in Cdh23 Mutant Mice

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2016 Nov 25

PMID 27882946

Citations 21

Authors

Juan Hu

Bo Li

Luke Apisa

Heping Yu

Shami Entenman

Min Xu

Ruben Stepanyan

Bo-Jhih Guan

Ulrich Muller

Maria Hatzoglou

Qing Yin Zheng

Affiliations

Soon will be listed here.

Abstract

Hearing loss is one of the most common sensory impairments in humans. Mouse mutant models helped us to better understand the mechanisms of hearing loss. Recently, we have discovered that the erlong (erl) mutation of the cadherin23 (Cdh23) gene leads to hearing loss due to hair cell apoptosis. In this study, we aimed to reveal the molecular pathways upstream to apoptosis in hair cells to exploit more effective therapeutics than an anti-apoptosis strategy. Our results suggest that endoplasmic reticulum (ER) stress is the earliest molecular event leading to the apoptosis of hair cells and hearing loss in erl mice. We also report that the ER stress inhibitor, Salubrinal (Sal), could delay the progression of hearing loss and preserve hair cells. Our results provide evidence that therapies targeting signaling pathways in ER stress development prevent hair cell apoptosis at an early stage and lead to better outcomes than those targeting downstream factors, such as tip-link degeneration and apoptosis.

Citing Articles

Insights into the molecular underlying mechanisms and therapeutic potential of endoplasmic reticulum stress in sensorineural hearing loss.

Li G, Yang H, Zhang P, Guo Y, Yuan L, Xu S Front Mol Neurosci. 2025; 17:1443401.

PMID: 39744539 PMC: 11688397. DOI: 10.3389/fnmol.2024.1443401.

Mutations in unfolded protein response regulator ATF6 cause hearing and vision loss syndrome.

Lee E, Kim K, Diaz-Aguilar M, Min H, Chavez E, Steinbergs K J Clin Invest. 2024; 135(3).

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Caffeine Ameliorates Age-Related Hearing Loss by Downregulating the Inflammatory Pathway in Mice.

Zhang X, Cao R, Li C, Zhao H, Zhang R, Che J Otol Neurotol. 2024; 45(3):227-237.

PMID: 38320571 PMC: 10922330. DOI: 10.1097/MAO.0000000000004098.

Peroxisome Deficiency in Cochlear Hair Cells Causes Hearing Loss by Deregulating BK Channels.

Fu X, Wan P, Lu L, Wan Y, Liu Z, Hong G Adv Sci (Weinh). 2023; 10(20):e2300402.

PMID: 37171794 PMC: 10369297. DOI: 10.1002/advs.202300402.

Ginsenoside Rc from Panax Ginseng Ameliorates Palmitate-Induced UB/OC-2 Cochlear Cell Injury.

Gill N, Dowker-Key P, Hubbard K, Voy B, Whelan J, Hedrick M Int J Mol Sci. 2023; 24(8).

PMID: 37108509 PMC: 10139021. DOI: 10.3390/ijms24087345.

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