Targeting Ferroptosis in Sensorineural Hearing Loss: A Mechanistic Review of Therapeutic Opportunities

Ferroptosis, an iron-dependent form of regulated cell death, is emerging as a critical pathogenic mechanism and a highly promising therapeutic target in sensorineural hearing loss (SNHL). The irreversible loss of auditory hair cells, the hallmark of SNHL, creates an urgent need for novel therapeutic strategies. This review provides a translational perspective on ferroptosis, connecting its core molecular machinery to tangible opportunities for otoprotection. We systematically analyze three key targetable nodes: the iron metabolic pathways that fuel the process; the lipid peroxidation machinery that executes membrane damage; and the collapse of the System Xc^--GSH-GPX4 antioxidant axis. By framing the disease mechanism through these actionable targets, we highlight a clear rationale for developing new hearing preservation therapies. We conclude by surveying the most promising pharmacological approaches, including iron chelators, radical-trapping antioxidants, and bioactive natural products, offering a strategic roadmap for future drug discovery in audiology.