{"id":"doi:10.1002/mco2.71019","kind":"review","title":"Myelination and Remyelination in Peripheral Nerve Injury: Mechanisms, Regulation, and Therapeutic Perspectives","authors":["Huang LX","Sun T","Zhao YB","Wu ZM","Sun J","Li MY","Huo QY","Ou YM","Liang QT","Ling C","Zhang BY","Chen C","Guo Y","Wang H"],"author_count":14,"year":2026,"published":"2026-10-11","venue":"MedComm","cited_by":0,"doi":"10.1002/mco2.71019","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1002/mco2.71019","archive_url":"https://space-kitty.com/papers/doi:10.1002/mco2.71019","updated":null,"pmid":"42865824","pmcid":null,"openalex_id":null,"pdf_url":null,"abstract":"Peripheral nerve injury (PNI) affects 13-23 individuals per 100,000 annually, and functional recovery hinges on faithful remyelination of regenerating axons by Schwann cells (SCs). This review integrates the complete molecular logic governing the transition from injury-induced SC plasticity to mature myelin regeneration. The hierarchical transcriptional program-from SOX10 pioneer factor engagement through OCT6-mediated promyelinating transition to KROX20/EGR2-driven activation of compact myelin genes-and the instructive role of axonal Neuregulin-1 Type III signaling are dissected. Wallerian degeneration via the NMNAT2-SARM1-mediated axon degeneration cascade, c-JUN-dependent SC reprogramming, and the epigenetic and noncoding RNA mechanisms that re-engage myelination are examined. The immune microenvironment is considered as a temporally layered network in which macrophage polarization, macrophage-to-myofibroblast transition, and regulatory T cell activity coordinate the transition from inflammation to repair. Finally, this review critically evaluates emerging therapeutic strategies-including Neuregulin-1 supplementation, SC transplantation, nerve guidance conduits, electrical stimulation, and senolytic clearance of aged SCs-and argues that rationally sequenced combination therapies will be required to achieve transformative improvements in functional recovery after severe PNI. This review provides a mechanistic roadmap for designing next-generation regenerative strategies aimed at restoring saltatory conduction.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Myelination and Remyelination in Peripheral Nerve Injury: Mechanisms, Regulation, and Therapeutic Perspectives\" by Huang LX, Sun T, Zhao YB et al., https://doi.org/10.1002/mco2.71019, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"aging-longevity","name":"Biology of Aging & Longevity","domain_slug":"medicine"}],"cited_in_dossiers":[]}