Myelination of the nervous system: mechanisms and functions

Annu Rev Cell Dev Biol. 2014;30:503-33. doi: 10.1146/annurev-cellbio-100913-013101.


Myelination of axons in the nervous system of vertebrates enables fast, saltatory impulse propagation, one of the best-understood concepts in neurophysiology. However, it took a long while to recognize the mechanistic complexity both of myelination by oligodendrocytes and Schwann cells and of their cellular interactions. In this review, we highlight recent advances in our understanding of myelin biogenesis, its lifelong plasticity, and the reciprocal interactions of myelinating glia with the axons they ensheath. In the central nervous system, myelination is also stimulated by axonal activity and astrocytes, whereas myelin clearance involves microglia/macrophages. Once myelinated, the long-term integrity of axons depends on glial supply of metabolites and neurotrophic factors. The relevance of this axoglial symbiosis is illustrated in normal brain aging and human myelin diseases, which can be studied in corresponding mouse models. Thus, myelinating cells serve a key role in preserving the connectivity and functions of a healthy nervous system.

Keywords: Schwann cell; axoglial signaling; brain energy metabolism; myelin sheath; neural plasticity; oligodendrocyte.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Axons / physiology
  • Central Nervous System / metabolism
  • Charcot-Marie-Tooth Disease / metabolism
  • Charcot-Marie-Tooth Disease / pathology
  • Cytoskeleton / ultrastructure
  • Demyelinating Diseases / metabolism
  • Demyelinating Diseases / pathology
  • Glucose / metabolism
  • Humans
  • Inflammation
  • Leukoencephalopathies / metabolism
  • Leukoencephalopathies / pathology
  • Mice
  • Microscopy, Electron
  • Myelin Proteins / physiology
  • Myelin Sheath / physiology*
  • Neuronal Plasticity
  • Oligodendroglia / physiology
  • Peripheral Nervous System / metabolism
  • Schwann Cells / physiology
  • Synaptic Transmission / physiology


  • Myelin Proteins
  • Aspartic Acid
  • Adenosine Triphosphate
  • N-acetylaspartate
  • Glucose