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Advanced Glycation Endproducts Are Increased in the Animal Model of Multiple Sclerosis but Cannot Be Reduced by Pyridoxamine Treatment or Glyoxalase 1 Overexpression

1
Department of Immunology and Biochemistry, Biomedical Research Institute, Hasselt University, Martelarenlaan 42 3500 Hasselt, Belgium
2
Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 ER Maastricht, The Netherlands
3
Division of Molecular Medicine and Therapy, Tohoku University Graduate School of Medicine, 980-8577 Sendai, Japan
4
Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, 6229 ER Maastricht, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(5), 1311; https://doi.org/10.3390/ijms19051311
Received: 26 March 2018 / Revised: 20 April 2018 / Accepted: 24 April 2018 / Published: 27 April 2018
(This article belongs to the Special Issue Glyoxalase System in Health and Disease 2017)
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Abstract

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS). The immune response in MS patients leads to the infiltration of immune cells in the CNS and their subsequent activation. Immune cell activation induces a switch towards glycolysis. During glycolysis, the dicarbonyl product methylglyoxal (MGO) is produced. MGO is a glycating agent that can rapidly form advanced glycation endproducts (AGEs). In turn, AGEs are able to induce inflammatory responses. The glyoxalase system is the endogenous defense system of the body to reduce the burden of MGO thereby reducing AGE formation. This system consists of glyoxalase-1 and glyoxalase-2 which are able to detoxify MGO to D-lactate. We investigated whether AGE levels are induced in experimental autoimmune encephalitis (EAE), an inflammatory animal model of MS. Twenty seven days post EAE induction, MGO and AGE (Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL), 5-hydro-5-methylimidazolone (MG-H1)) levels were significantly increased in the spinal cord of mice subjected to EAE. Yet, pyridoxamine treatment and glyoxalase-1 overexpression were unable to counteract AGE production during EAE and did not influence the clinical course of EAE. In conclusion, AGEs levels increase during EAE in the spinal cord, but AGE-modifying treatments do not inhibit EAE-induced AGE production and do not affect disease progression. View Full-Text
Keywords: advanced glycation endproducts; pyridoxamine; glyoxalase-1; experimental autoimmune encephalomyelitis; multiple sclerosis advanced glycation endproducts; pyridoxamine; glyoxalase-1; experimental autoimmune encephalomyelitis; multiple sclerosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Wetzels, S.; Wouters, K.; Miyata, T.; Scheijen, J.L.J.M.; Hendriks, J.J.A.; Schalkwijk, C.G.; Vanmierlo, T. Advanced Glycation Endproducts Are Increased in the Animal Model of Multiple Sclerosis but Cannot Be Reduced by Pyridoxamine Treatment or Glyoxalase 1 Overexpression. Int. J. Mol. Sci. 2018, 19, 1311.

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