Association of a Marker of N-Acetylglucosamine With Progressive Multiple Sclerosis and Neurodegeneration

Abstract

Key Points Question Is the serum concentration of N -acetylglucosamine (GlcNAc) altered in patients with multiple sclerosis? Findings This cross-sectional study found that patients with a progressive multiple sclerosis subtype and more severe disease have reduced serum levels of a marker of GlcNAc. In addition, GlcNAc is a rate-limiting substrate for N -glycan branching, which has been shown to regulate immunoactivity and myelination. Meaning This study suggests that GlcNAc and N -glycan branching are associated with multiple sclerosis in general and progressive multiple sclerosis in particular.

The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency

“…2) A decrease in N-Ac-Glu and N-Ac-Glu-6P levels in the serum, brain and kidneys was observed. These two metabolites work in the hexosamine biosynthetic pathway and are involved in O-linked glycosylation, which has been associated with the regulation of mitochondrial function [ 65 ], and is related to neuroinflammation and myelinization [ 66 , 67 ]. 3) A decrease in the levels of SERPINA3, MASP1, COL1A1 and AI182371 and an increase in PZP was observed.…”

Age-associated impairment of T cell immunity is linked to sex-dimorphic elevation of N-glycan branching

“…Interestingly, using targeted liquid chromatographytandem mass-spectrometry (LC-MS/MS) to assess GlcNAc and its stereoisomers (N-acetylhexosamines or HexNAc) in human serum revealed marked increases with age in both females and males (Fig. 6c,d) 48,49 . However, endogenous serum HexNAc levels correlated positively with N-glycan branching in CD4 + T N cells of females but not of males (Fig.…”

The Crossroads of Glycoscience, Infection, and Immunology

“…The mechanism involves glycan-binding proteins called galectins that, when N-glycans are sufficiently abundant and branched, form a cell surface lattice of immune regulatory molecules on both T cells and B cells ( Mortales et al, 2020 ). Insufficient branching of N-glycans can result in autoimmune sensitivity, for example, in multiple sclerosis and autoimmune diabetes ( Brandt et al, 2021 ). Remarkably, oral administration of the sugar N-acetylglucosamine in human subjects increases N-glycan branching, raising the hope that dietary supplementation may reduce autoimmunity.…”