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| Item Type: | Article |
|---|---|
| Title: | N-acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation |
| Creators Name: | Sy, M. and Brandt, A.U. and Lee, S.U. and Newton, B. L. and Pawling, J. and Golzar, A. and Rahman, A.A. and Yu, Z. and Cooper, G. and Scheel, M. and Paul, F. and Dennis, J.W. and Demetriou, M. |
| 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. |
| Keywords: | N-glycan Branching, N-acetylglucosamine, Oligodendrocytes, Myelination, Myelin Repair, Multiple Sclerosis, Animals, Mice |
| Source: | Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Volume: | 295 |
| Number: | 51 |
| Page Range: | 17413-17424 |
| Date: | 18 December 2020 |
| Official Publication: | https://doi.org/10.1074/jbc.RA120.015595 |
| PubMed: | View item in PubMed |
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