Progress in Research on the Mechanisms and Therapeutic Targets of Ferroptosis in Peripheral Nerve Injury and Repair

Abstract Repair after peripheral nerve injury (PNI) faces major obstacles due to microenvironmental imbalance and neuronal loss. Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, has emerged as a key pathological event in PNI, linking oxidative stress, mitochondrial dysfunction, and inflammation to regenerative failure. Targeting ferroptosis protects vital cells—such as Schwann cells and neurons—and ameliorates the regenerative niche, offering a promising therapeutic strategy. This review elucidates the mechanisms of ferroptosis in PNI, detailing its roles in Schwann cells, dorsal root ganglion neurons, and macrophages via core pathways including Nrf2/HO-1/GPX4 and ACSL4. We further evaluate current intervention strategies and their therapeutic efficacy. This synthesis provides novel insights into PNI pathology and guides the development of innovative treatments.