A glycolytic shift in Schwann cells supports injured axons

Nat Neurosci. 2020 Oct;23(10):1215-1228. doi: 10.1038/s41593-020-0689-4. Epub 2020 Aug 17.


Axon degeneration is a hallmark of many neurodegenerative disorders. The current assumption is that the decision of injured axons to degenerate is cell-autonomously regulated. Here we show that Schwann cells (SCs), the glia of the peripheral nervous system, protect injured axons by virtue of a dramatic glycolytic upregulation that arises in SCs as an inherent adaptation to axon injury. This glycolytic response, paired with enhanced axon-glia metabolic coupling, supports the survival of axons. The glycolytic shift in SCs is largely driven by the metabolic signaling hub, mammalian target of rapamycin complex 1, and the downstream transcription factors hypoxia-inducible factor 1-alpha and c-Myc, which together promote glycolytic gene expression. The manipulation of glial glycolytic activity through this pathway enabled us to accelerate or delay the degeneration of perturbed axons in acute and subacute rodent axon degeneration models. Thus, we demonstrate a non-cell-autonomous metabolic mechanism that controls the fate of injured axons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Axons / pathology*
  • Cells, Cultured
  • Female
  • Ganglia, Spinal / metabolism*
  • Ganglia, Spinal / pathology
  • Glycolysis*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • Mice
  • Nerve Degeneration / metabolism*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Schwann Cells / metabolism*
  • Schwann Cells / pathology
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism


  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Proto-Oncogene Proteins c-myc
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases