title: Methylglyoxal-Derived Advanced Glycation Endproducts in Multiple Sclerosis.
abstract: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). The activation of inflammatory cells is crucial for the development of MS and is shown to induce intracellular glycolytic metabolism in pro-inflammatory microglia and macrophages, as well as CNS-resident astrocytes. Advanced glycation endproducts (AGEs) are stable endproducts formed by a reaction of the dicarbonyl compounds methylglyoxal (MGO) and glyoxal (GO) with amino acids in proteins, during glycolysis. This suggests that, in MS, MGO-derived AGEs are formed in glycolysis-driven cells. MGO and MGO-derived AGEs can further activate inflammatory cells by binding to the receptor for advanced glycation endproducts (RAGE). Recent studies have revealed that AGEs are increased in the plasma and brain of MS patients. Therefore, AGEs might contribute to the inflammatory status in MS. Moreover, the main detoxification system of dicarbonyl compounds, the glyoxalase system, seems to be affected in MS patients, which may contribute to high MGO-derived AGE levels. Altogether, evidence is emerging for a contributing role of AGEs in the pathology of MS. In this review, we provide an overview of the current knowledge on the involvement of AGEs in MS.
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 Maastricht, The Netherlands. suzan.wetzels@uhasselt.be.|Department of Immunology and Biochemistry, Biomedical Research Institute, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium. suzan.wetzels@uhasselt.be.
authors.forename: Suzan
authors.initials: S
authors.lastname: Wetzels
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 Maastricht, The Netherlands. kristiaan.wouters@maastrichtuniversity.nl.
authors.forename: Kristiaan
authors.initials: K
authors.lastname: Wouters
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 Maastricht, The Netherlands. c.schalkwijk@maastrichtuniversity.nl.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: Department of Immunology and Biochemistry, Biomedical Research Institute, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium. tim.vanmierlo@uhasselt.be.
authors.forename: Tim
authors.initials: T
authors.lastname: Vanmierlo
authors.affiliation: Department of Immunology and Biochemistry, Biomedical Research Institute, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium. jerome.hendriks@uhasselt.be.
authors.forename: Jerome J A
authors.initials: JJ
authors.lastname: Hendriks
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007113:Immunity, Innate; D015227:Lipid Peroxidation; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011765:Pyruvaldehyde / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011765:Pyruvaldehyde
keywords: advanced glycation endproducts; glyoxalase system; methylglyoxal; multiple sclerosis; receptor for advanced glycation endproduct