Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 77, Issue 20, Pages 3977-3989Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-020-03516-9
Keywords
Schwann cell; Plasticity; Reprogramming; Chromatin remodeling enzymes; Transcription factors; Signaling pathways; Nerve injury and repair; Axonal regeneration; Remyelination
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Funding
- Projekt DEAL
- International Foundation for Research in Paraplegia (IRP)
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The great plasticity of Schwann cells (SCs), the myelinating glia of the peripheral nervous system (PNS), is a critical feature in the context of peripheral nerve regeneration following traumatic injuries and peripheral neuropathies. After a nerve damage, SCs are rapidly activated by injury-induced signals and respond by entering the repair program. During the repair program, SCs undergo dynamic cell reprogramming and morphogenic changes aimed at promoting nerve regeneration and functional recovery. SCs convert into a repair phenotype, activate negative regulators of myelination and demyelinate the damaged nerve. Moreover, they express many genes typical of their immature state as well as numerous de-novo genes. These genes modulate and drive the regeneration process by promoting neuronal survival, damaged axon disintegration, myelin clearance, axonal regrowth and guidance to their former target, and by finally remyelinating the regenerated axon. Many signaling pathways, transcriptional regulators and epigenetic mechanisms regulate these events. In this review, we discuss the main steps of the repair program with a particular focus on the molecular mechanisms that regulate SC plasticity following peripheral nerve injury.
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