The ubiquitin-proteasome system in normal hearing and deafness

Pouyo, Ronald; Chung, Keshi; Delacroix, Laurence; Malgrange, Brigitte

doi:10.1016/j.heares.2021.108366

Cited by 4 publications

(3 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ubiquitination is a three-step process with ubiquitin activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3) involved respectively in each step. Pouyo et al 10 have recently reviewed the major roles of UPS actors in cochlear development and function, otoprotection and mouse, or human deafness and presbycusis. However, related research is still scarce and the precise role of the UPS in hearing loss remains unclear.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

GRAIL gene knockout mice protect against aging-related and noise-induced hearing loss

Chuang,

Wang,

Chen

et al. 2023

Journal of the Chinese Medical Association

View full text Add to dashboard Cite

Background: Hearing loss is a global health issue and its etiopathologies involve complex molecular pathways. The ubiquitin-proteasome system has been reported to be associated with cochlear development and hearing loss. The gene related to anergy in lymphocytes (GRAIL), as an E3 ubiquitin ligase, has not, as yet, been examined in aging-related and noise-induced hearing loss mice models. Methods: This study used wild-type (WT) and GRAIL knockout (KO) mice to examine cochlear hair cells and synaptic ribbons using immunofluorescence staining. The hearing in WT and KO mice was detected using auditory brainstem response. Gene expression patterns were compared using RNA-sequencing to identify potential targets during the pathogenesis of noise-induced hearing loss in WT and KO mice. Results: At the 12-month follow-up, GRAIL KO mice had significantly less elevation in threshold level and immunofluorescence staining showed less loss of outer hair cells and synaptic ribbons in the hook region compared with GRAIL WT mice. At Days 1, 14, and 28 after noise exposure, GRAIL KO mice had significantly less elevation in threshold level than WT mice. After noise exposure, GRAIL KO mice showed less loss of outer hair cells in the cochlear hook and basal regions compared with WT mice. Moreover, immunofluorescence staining showed less loss of synaptic ribbons in the hook regions of GRAIL KO mice than of WT mice. RNA-seq analysis results showed significant differences in CCL19, CCL21, IL25, GPX6 and NOX1 genes after noise exposure. Conclusion: The present data demonstrated that GRAIL deficiency protects against aging-related and noise-induced hearing loss. The mechanism involved needs to be further clarified from the potential association with synaptic modulation, inflammation, and oxidative stress.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The ubiquitin-proteasome system (UPS) has been reported to be associated with cochlear development and hearing loss. 10 As an important regulator of synaptic plasticity [11][12][13] and being activated in the cochlea following excessive noise exposure, 14 the UPS is essential for cochlear development and maintenance.…”

Section: Introductionmentioning

confidence: 99%

GRAIL gene knockout mice protect against aging-related and noise-induced hearing loss

Chuang,

Wang,

Chen

et al. 2023

Journal of the Chinese Medical Association

View full text Add to dashboard Cite

show abstract

“…Mutations in a gene‐related deafness lead to changes in the function of the protein it encodes, resulting in deafness. In addition, abnormal protein synthesis and degradation caused by changes in epigenetic regulation or physiological state can also lead to impaired hearing function (Kuo et al, 2021; Pouyo et al, 2021). In recent years, researchers have focused on the link between ARHL and changes in various of deafness‐related genes and their encoded proteins.…”

Section: Introductionmentioning

confidence: 99%

Degradation of cochlear Connexin26 accelerate the development of age‐related hearing loss

Xu,

Chen,

Bai

et al. 2023

Aging Cell

View full text Add to dashboard Cite

The GJB2 gene, encoding Connexin26 (Cx26), is one of the most common causes of inherited deafness. Clinically, mutations in GJB2 cause congenital deafness or late‐onset progressive hearing loss. Recently, it has been reported that Cx26 haploid deficiency accelerates the development of age‐related hearing loss (ARHL). However, the roles of cochlear Cx26 in the hearing function of aged animals remain unclear. In this study, we revealed that the Cx26 expression was significantly reduced in the cochleae of aged mice, and further explored the underlying molecular mechanism for Cx26 degradation. Immunofluorescence co‐localization results showed that Cx26 was internalized and degraded by lysosomes, which might be one of the important ways for Cx26 degradation in the cochlea of aged mice. Currently, whether the degradation of Cx26 in the cochlea leads directly to ARHL, as well as the mechanism of Cx26 degradation‐related hearing loss are still unclear. To address these questions, we generated mice with Cx26 knockout in the adult cochlea as a model for the natural degradation of Cx26. Auditory brainstem response (ABR) results showed that Cx26 knockout mice exhibited high‐frequency hearing loss, which gradually progressed over time. Pathological examination also revealed the degeneration of hair cells and spiral ganglions, which is similar to the phenotype of ARHL. In summary, our findings suggest that degradation of Cx26 in the cochlea accelerates the occurrence of ARHL, which may be a novel mechanism of ARHL.

show abstract

Understanding neurodevelopmental proteasomopathies as new rare disease entities: A review of current concepts, molecular biomarkers, and perspectives

Cuinat,

Bézieau,

Deb

et al. 2024

Genes & Diseases

View full text Add to dashboard Cite

The ubiquitin-proteasome system in normal hearing and deafness

Cited by 4 publications

References 124 publications

GRAIL gene knockout mice protect against aging-related and noise-induced hearing loss

GRAIL gene knockout mice protect against aging-related and noise-induced hearing loss

Degradation of cochlear Connexin26 accelerate the development of age‐related hearing loss

Understanding neurodevelopmental proteasomopathies as new rare disease entities: A review of current concepts, molecular biomarkers, and perspectives

Contact Info

Product

Resources

About