Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons

Greg J. Duncan, Tyrell J. Simkins, Ben Emery

Research output: Contribution to journalReview articlepeer-review

45 Scopus citations


The myelination of axons by oligodendrocytes is a highly complex cell-to-cell interaction. Oligodendrocytes and axons have a reciprocal signaling relationship in which oligodendrocytes receive cues from axons that direct their myelination, and oligodendrocytes subsequently shape axonal structure and conduction. Oligodendrocytes are necessary for the maturation of excitatory domains on the axon including nodes of Ranvier, help buffer potassium, and support neuronal energy metabolism. Disruption of the oligodendrocyte-axon unit in traumatic injuries, Alzheimer’s disease and demyelinating diseases such as multiple sclerosis results in axonal dysfunction and can culminate in neurodegeneration. In this review, we discuss the mechanisms by which demyelination and loss of oligodendrocytes compromise axons. We highlight the intra-axonal cascades initiated by demyelination that can result in irreversible axonal damage. Both the restoration of oligodendrocyte myelination or neuroprotective therapies targeting these intra-axonal cascades are likely to have therapeutic potential in disorders in which oligodendrocyte support of axons is disrupted.

Original languageEnglish (US)
Article number653101
JournalFrontiers in Cell and Developmental Biology
StatePublished - Mar 8 2021


  • Wallerian degeneration
  • axonal degeneration
  • demyelination
  • mitochondria
  • multiple sclerosis
  • oligodendrocyte
  • remyelination

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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