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N-Acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation.

  • Author(s): Sy, Michael
  • Brandt, Alexander U
  • Lee, Sung-Uk
  • Newton, Barbara L
  • Pawling, Judy
  • Golzar, Autreen
  • Rahman, Anas A
  • Yu, Zhaoxia
  • Cooper, Graham
  • Scheel, Michael
  • Paul, Friedemann
  • Dennis, James W
  • Demetriou, Michael
  • et al.
Abstract

Myelination plays an important role in cognitive development and in demyelinating diseases like multiple sclerosis (MS), where failure of re-myelination promotes permanent neuro-axonal damage.  Modification of cell surface receptors with branched N-glycans coordinates cell growth and differentiation by controlling glycoprotein clustering, signaling and endocytosis. N-acetylglucosamine (GlcNAc) is a rate-limiting metabolite for N-glycan branching. Here we report that GlcNAc and N-glycan branching trigger oligodendrogenesis from precursor cells by inhibiting PDGF receptor-α cell endocytosis. Supplying oral GlcNAc to lactating mice drives primary myelination in newborn pups via secretion in breast milk, while genetically blocking N-glycan branching markedly inhibits primary myelination. In adult mice with toxin (cuprizone) induced demyelination, oral GlcNAc prevents neuro-axonal damage by driving myelin repair. In MS patients, endogenous serum GlcNAc levels inversely correlated with imaging measures of demyelination and microstructural damage.   Our data identifies N-glycan branching and GlcNAc as critical regulators of primary myelination and myelin repair and suggests oral GlcNAc may be neuro-protective in demyelinating diseases like MS.

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