AUTHOR=Wetzels Suzan , Vanmierlo Tim , Scheijen Jean L. J. M. , van Horssen Jack , Amor Sandra , Somers Veerle , Schalkwijk Casper G. , Hendriks Jerome J. A. , Wouters Kristiaan TITLE=Methylglyoxal-Derived Advanced Glycation Endproducts Accumulate in Multiple Sclerosis Lesions JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00855 DOI=10.3389/fimmu.2019.00855 ISSN=1664-3224 ABSTRACT=
Multiple sclerosis (MS) is a demyelinating autoimmune disease in which innate and adaptive immune cells infiltrate the central nervous system (CNS) and damage the myelin sheaths surrounding the axons. Upon activation, infiltrated macrophages, CNS-resident microglia, and astrocytes switch their metabolism toward glycolysis, resulting in the formation of α-dicarbonyls, such as methylglyoxal (MGO) and glyoxal (GO). These potent glycating agents lead to the formation of advanced glycation endproducts (AGEs) after reaction with amino acids. We hypothesize that AGE levels are increased in MS lesions due to the inflammatory activation of macrophages and astrocytes. First, we measured tissue levels of AGEs in brain samples of MS patients and controls. Analysis of MS patient and non-demented control (NDC) specimens showed a significant increase in protein-bound Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1), the major AGE, compared to white matter of NDCs (107 ± 11 vs. 154 ± 21,