| First Author | Sy M | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 51 | Pages | 17413-17424 |
| PubMed ID | 33453988 | Mgi Jnum | J:330662 |
| Mgi Id | MGI:6802312 | Doi | 10.1074/jbc.RA120.015595 |
| Citation | Sy M, et al. (2020) N-acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation. J Biol Chem 295(51):17413-17424 |
| abstractText | Myelination plays an important role in cognitive development and in demyelinating diseases like multiple sclerosis (MS), where failure of remyelination 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. 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 platelet-derived growth factor receptor-alpha cell endocytosis. Supplying oral GlcNAc to lactating mice drives primary myelination in newborn pups via secretion in breast milk, whereas 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 identify N-glycan branching and GlcNAc as critical regulators of primary myelination and myelin repair and suggest that oral GlcNAc may be neuroprotective in demyelinating diseases like MS. |
