Pathological mechanisms of connexin26-related hearing loss: Potassium recycling, ATP-calcium signaling, or energy supply?

Frontiers in Molecular Neuroscience, Год журнала: 2022, Номер 15

Опубликована: Сен. 15, 2022

Hereditary deafness is one of the most common human birth defects. GJB2 gene mutation genetic etiology. Gap junction protein 26 (connexin26, Cx26) encoded by gene, which responsible for intercellular substance transfer and signal communication, plays a critical role in hearing acquisition maintenance. The auditory character different Connexin26 transgenic mice models can be classified into two types: profound congenital late-onset progressive loss. Recent studies demonstrated that there are pathological changes including endocochlear potential reduction, active cochlear amplification impairment, developmental disorders, so on, connexin26 deficiency mice. Here, this review summarizes three main hypotheses to explain mechanisms connexin26-related loss: potassium recycling disruption, adenosine-triphosphate-calcium signaling propagation energy supply dysfunction. Elucidating underlying loss help develop new protective therapeutic strategies deafness. It worthy further study on detailed cellular molecular upstream modify connexin (channel) function.

Язык: Английский

---

Cytomembrane Trafficking Pathways of Connexin 26, 30, and 43

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(12), С. 10349 - 10349

Опубликована: Июнь 19, 2023

The connexin gene family is the most prevalent that contributes to hearing loss. Connexins 26 and 30, encoded by GJB2 GJB6, respectively, are abundantly expressed connexins in inner ear. Connexin 43, which GJA1, appears be widely various organs, including heart, skin, brain, mutations arise GJB2, GJA1 can all result comprehensive or non-comprehensive genetic deafness newborns. As it predicted include at least 20 isoforms humans, biosynthesis, structural composition, degradation of must precisely regulated so gap junctions properly operate. Certain possessing a faulty subcellular localization, failing transport cell membrane preventing junction formation, ultimately leading dysfunction In this review, we provide discussion models for 30 26, affecting trafficking pathways these connexins, existing controversies molecules involved their functions. This review contribute new way understanding etiological principles finding therapeutic strategies hereditary deafness.

Язык: Английский

---

Schisandrin B protect inner hair cells from cisplatin by inhibiting celluar oxidative stress and apoptosis

Toxicology in Vitro, Год журнала: 2024, Номер 99, С. 105852 - 105852

Опубликована: Май 23, 2024

Язык: Английский

---

Bioinformatics approach reveals the critical role of inflammation-related genes in age-related hearing loss

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 21, 2025

Age-related hearing loss (ARHL) is the most prevalent sensory impairment in elderly. However, pathogenesis of ARHL remains unclear. This study was aimed to explore potential inflammation-related genes and suggest novel therapeutic targets for this condition. Initially, a total 105 Inflammatory related differentially expressed (IRDEGs) were obtained by overlapping from GSE49522 GSE49543 datasets with genes. The IRDEGs mainly enriched MAPK, PI3K-Akt, Hippo JAK-STAT pathways analysis Gene Ontology Kyoto Encyclopedia Genes Genomes. We then identified 10 key including Alox5ap, Chil1, Clec7a, Dysf, Fcgr3, etc. using Least absolute shrinkage selection operator regression converted them into human ROC curve indicated that Alox5ap expression presented high accuracy distinguishing between different groups. By CIBERSORT algorithm, 8 humanized correlated infiltration abundance 3 immune cells. Finally, it showed significantly more effective compared other variables diagnostic model ARHL. suggests inflammation might play role development ARHL, providing deeper understanding underlying causes disease.

Язык: Английский

---

Identification of Potential Therapeutic Targets for Sensorineural Hearing Loss and Evaluation of Drug Development Potential Using Mendelian Randomization Analysis

Bioengineering, Год журнала: 2025, Номер 12(2), С. 126 - 126

Опубликована: Янв. 29, 2025

Background: Sensorineural hearing loss (SNHL) is a major contributor to impairment, yet effective therapeutic options remain elusive. Mendelian randomization (MR) has proven valuable for drug repurposing and identifying new targets. This study aims pinpoint novel treatment targets SNHL, exploring their pathophysiological roles potential adverse effects. Methods: research utilized the UKB-PPP database access cis-protein quantitative trait locus (cis-pQTL) data, with SNHL data sourced from FinnGen as endpoint MR causal analysis of Colocalization was employed determine whether risk protein expression share common SNPs. A phenotype-wide association conducted assess side effects these Drug prediction molecular docking were subsequently used evaluate identified Results: Four target proteins significantly associated sensorineural determined by co-localization analysis. These include LATS1, TEF, LMNB2, OGFR shown have fewer when acting on Genes are primarily implicated in Hippo signaling pathway, cell–cell adhesion, various binding regulatory activities involved regulation cell proliferation apoptosis. Next, drugs screened DsigDB docking, top 10 selected based p-value. Among them, atrazine CTD 00005450 most likely target, followed ampyrone HL60 DOWN genistein 00007324. In addition, could be intervened multiple drugs; however, TEF. Conclusion: successfully four promising which clinical trials minimal findings streamline development potentially reducing costs time pharmaceutical development.

Язык: Английский

---

Mechanisms of congenital hearing loss caused by GJB2 gene mutations and current progress in gene therapy

Gene, Год журнала: 2025, Номер 946, С. 149326 - 149326

Опубликована: Фев. 11, 2025

Язык: Английский

---

Generation of kidney organoids derived from human expanded potential stem cells

Cells and Development, Год журнала: 2025, Номер unknown, С. 204025 - 204025

Опубликована: Апрель 1, 2025

Язык: Английский

---

Exploring the potential biomarkers and potential causality of Ménière disease based on bioinformatics and machine learning

Medicine, Год журнала: 2025, Номер 104(19), С. e42399 - e42399

Опубликована: Май 9, 2025

Meniere disease (MD) is a common inner ear disorder closely related to immune abnormalities, but research on the characteristic genes between MD and responses still insufficient. We employ bioinformatics machine learning predict potential biomarkers cells associated with MD, investigating Mendelian randomization causation providing new insight for early diagnosis, prevention, treatment of MD. obtained relevant data from GEO database using R, conducted differential gene analysis, performed weighted co-expression network analysis (WGCNA) identify Moreover, by integrating selection core PPI techniques, we predicted Simultaneously, infiltration identified key cell types. Finally, employed comprehensively evaluate causal relationship Through WGCNA, 550 enrichment predominantly focused pertinent diseases. The protein-protein interaction (PPI) screening 2 MD: CD5 AJUBA, 3 types T CD4 memory resting, gamma delta Dendritic activated. revealed 26 There AJUBA are while activated These offer insights

Язык: Английский

---

Advancements in inner ear development, regeneration, and repair through otic organoids

Current Opinion in Genetics & Development, Год журнала: 2022, Номер 76, С. 101954 - 101954

Опубликована: Июль 16, 2022

The vertebrate inner ear contains a diversity of unique cell types arranged in particularly complex 3D cytoarchitecture. Both these features are integral to the proper development, function, and maintenance hearing balance. Since elucidation timing delivery signaling molecules produce sensory cells, supporting neurons from human induced pluripotent stem we have entered revolution using organ-like ‘otic organoid’ cultures explore specific genetic programs, developmental rules, potential therapeutics. This review aims highlight selection reviews primary research papers past two years particular merit that use otic organoids investigate broadly defined topics reprogramming, regeneration, repair.

Язык: Английский

---

Development of the inner ear and regeneration of hair cells after hearing impairment

Fundamental Research, Год журнала: 2023, Номер 5(1), С. 203 - 214

Опубликована: Ноя. 21, 2023

Hearing loss, as a sensory disorder, is the most common occurrence among humans, which has received increasing attention from society. It mainly caused by damage of inner ear hair cells (HCs) or degeneration spiral ganglion neurons. In mammals, cochlear HCs cannot regenerate naturally after injury, leading to irreversible hearing loss. Therefore, are essential for protection. recent years, protection drug-related ototoxicity, stem cells, gene therapy, new materials, and signal regulation have become important ways develop regeneration strategies HCs. An in-depth study causes development impairment loss effective prevention, discovery, treatment deafness great significance. This review aimed analyze summarize related factors injury research progress injury.

Язык: Английский

---