期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 295, 期 51, 页码 17413-17424出版社
ELSEVIER
DOI: 10.1074/jbc.RA120.015595
关键词
N-glycan branching; N-acetylglucosamine; oligodendrocytes; myelination; myelin repair; multiple sclerosis; N-linked glycosylation; oligodendrocyte; myelin; metabolism; oligodendrocyte precursor cell
资金
- Marilyn Hilton innovator award
- NIAID National Institutes of Health [R01AT007452]
- NCCIH National Institutes of Health [R01AI144403]
- Deutsche Forschungsgemeinschaft [Exc. 257]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据