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Progress in Research on the Mechanisms and Therapeutic Targets of Ferroptosis in Peripheral Nerve Injury and Repair
Jian Ruan1,2, Xin-Kun He1,2, Song-Ou Zhang1,2
1Department of Hand Surgery, Ningbo No.6 Hospital, Ningbo, Zhejiang, China.
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.