Molecular mechanisms of apoptosis in sensorineural hearing loss: the role of BID, BAD, BAK, BCL-x genes

Background: Sensorineural hearing loss (SNHL) is a common pathology affecting over 1.5 billion people worldwide. Understanding the molecular mechanisms of apoptosis, particularly the role of BID, BAD, BAK, and BCL-x genes, is critical for developing effective treatment methods. Objective: To analyze current data on the effects of oxidative stress on the expression of BID, BAD, BAK, and BCL-x genes in the context of sensorineural hearing loss development. Materials and Methods: A systematic literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases for the period 2020-2025. The analysis included clinical, experimental, and review articles investigating the role of apoptosis genes in SNHL. A meta-analysis of the studied genes' expression data was performed. Results: Increased expression of proapoptotic genes BID, BAD, and BAK (FC >1.5) and decreased expression of the antiapoptotic gene BCL-x (FC ≈ 0.73) were found in patients with SNHL. Oxidative stress was identified as a key factor in activating apoptosis in hair cells. Combined therapy with antioxidants and apoptosis inhibitors showed potential in preserving up to 30% of functional auditory cells in early stages of SNHL. Conclusions: The study confirms the key role of BID, BAD, BAK, and BCL-x genes in SNHL pathogenesis and substantiates the promise of developing therapeutic strategies aimed at modulating these genes' expression and reducing oxidative stress.