Methylglyoxal-Derived Advanced Glycation Endproducts in Multiple Sclerosis

Suzan Wetzels, Kristiaan Wouters, Casper G Schalkwijk, Tim Vanmierlo, Jerome J. A. Hendriks*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Article number421
Number of pages15
JournalInternational journal of molecular sciences
Issue number2
Publication statusPublished - 15 Feb 2017


  • Adaptive Immunity
  • Advanced Glycosylation End Product-Specific Receptor
  • Animals
  • Glycolysis
  • Glycosylation End Products, Advanced
  • Humans
  • Immunity, Innate
  • Lipid Peroxidation
  • Multiple Sclerosis
  • Oxidation-Reduction
  • Oxidative Stress
  • Pyruvaldehyde
  • Journal Article
  • Review

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