# Myelination and Remyelination in Peripheral Nerve Injury: Mechanisms, Regulation, and Therapeutic Perspectives

Review · 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

- Archive id: doi:10.1002/mco2.71019
- Published: 2026-10-11
- Venue: MedComm
- DOI: https://doi.org/10.1002/mco2.71019
- PMID: 42865824
- Citations: 0
- Source URL: https://doi.org/10.1002/mco2.71019
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Biology of Aging & Longevity](https://space-kitty.com/topics/aging-longevity)

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