Summary: N-acetylglucosamine, a simple sugar found in breast milk, promotes remyelination in mouse models of multiple sclerosis. The findings could have implications for treating multiple sclerosis in humans.
Source: UC Irvine
N-acetylglucosamine, a simple sugar found in human breast milk and sold as an over-the-counter dietary supplement in the United States, promotes myelin repair in mouse models and correlates with myelination levels in multiple sclerosis patients according to a new University of California, Irvine-led study.
Published in the Journal of Biological Chemistry, the study also demonstrates that in mice, delivering N-acetylglucosamine orally to lactating mothers drove primary myelination in their nursing offspring. N-acetylglucosamine is a simple sugar that is metabolically attached to proteins at the cell surface to control cellular function.
“We found that N-acetylglucosamine activates myelin stem cells to promote primary myelination and myelin repair,” said Michael Demetriou, MD, PhD, FRCP(C), professor of neurology, microbiology and molecular genetics at UCI School of Medicine and leader of the study. “Our data raises the intriguing possibility that N-acetylglucosamine may be a simple therapy to promote myelin repair in multiple sclerosis patients”. Formal human studies will be required to test this theory.
The failure of robust re-myelination following inflammatory demyelination in multiple sclerosis leads to chronic disability and neurodegeneration. Myelin insulates the long, cable-like nerve cell branches called axons, and serves to increase the speed of electrical signal conduction between neurons. Myelination in the central nervous system also plays an important role in cognitive development during childhood.
“Interestingly, since N-acetylglucosamine is a major component of human breast milk but not baby formula, it may explain some of the cognitive function and myelination benefits realized by children fed breast milk as opposed to formula.” said Michael Sy, MD, PhD, assistant professor of neurology at UCI School of Medicine, co-director of the regional MS program at the VA Long Beach Healthcare System, and first author of the study.
Dr. med. Alexander Brandt, MD, who led the clinical parts of the study together with Dr. med. Friedemann Paul, MD, added, “The association of reduced N-acetylglucosamine serum levels with white matter changes in the brain of patients with multiple sclerosis suggests that N-acetyglucosamine deficiency may contribute to disease severity.”
At the time of the study, Brandt has been the head of the Translational Neuroimaging laboratory in the Clinical Neuroimmunology group at Charité – Universitätsmedizin Berlin, which is led by Paul. Brandt has since transitioned to the UCI School of Medicine as associate professor of neurology.
Formal clinical trials are required to test the applications identified in this study and are currently being pursued by the investigators.
Funding: This study was funded in part by a Marilyn Hilton Innovator Award, the National Institutes of Health and the German Research Foundation Excellence Initiative, NeuroCure.
N-Acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation
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.