Strategies for myelin regeneration: lessons learned from development

Myelin is crucial for fast signal transmission in the nervous system and also supports axon health. When myelin is damaged, as in diseases like multiple sclerosis, regenerating it is important for restoring nerve function and preventing further axon damage. Myelin disorders can occur in both children and adults, with similar mechanisms involved in developmental and adult myelin disorders. One such mechanism is the failure of oligodendrocyte progenitor cells (OPCs) to mature into myelin-producing cells. Factors that regulate myelin development, like the Notch signaling pathway and LINGO-1, can also limit myelin regeneration after injury. Understanding these factors is leading to new therapies for myelin regeneration.

• 1
  Myelin regeneration shares similarities with myelin development, involving OPC proliferation, migration, differentiation, and myelination, but remyelinated axons often have thinner myelin sheaths and different nodal domain cytoarchitecture.
• 2
  Inhibitory factors present during development, such as laminins, semaphorins, LINGO-1, and Notch-1, can be re-expressed in demyelination lesions, hindering remyelination. Targeting these factors may provide therapeutic benefits.
• 3
  Microglia/macrophages play a complex role in myelin regeneration by clearing myelin debris and secreting trophic factors, and therapies targeting these cells may offer new approaches for myelin regenerative therapy.