Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous\nsystem (CNS). The immune response in MS patients leads to the infiltration of immune cells in\nthe CNS and their subsequent activation. Immune cell activation induces a switch towards glycolysis.\nDuring glycolysis, the dicarbonyl product methylglyoxal (MGO) is produced. MGO is a glycating\nagent that can rapidly form advanced glycation endproducts (AGEs). In turn, AGEs are able to\ninduce inflammatory responses. The glyoxalase system is the endogenous defense system of the body\nto reduce the burden of MGO thereby reducing AGE formation. This system consists of glyoxalase-1\nand glyoxalase-2 which are able to detoxify MGO to D-lactate. We investigated whether AGE levels\nare induced in experimental autoimmune encephalitis (EAE), an inflammatory animal model of\nMS. Twenty seven days post EAE induction, MGO and AGE (N�µ-(carboxymethyl)lysine (CML),\nN�µ-(carboxyethyl)lysine (CEL), 5-hydro-5-methylimidazolone (MG-H1)) levels were significantly\nincreased in the spinal cord of mice subjected to EAE. Yet, pyridoxamine treatment and glyoxalase-1\noverexpression were unable to counteract AGE production during EAE and did not influence\nthe clinical course of EAE. In conclusion, AGEs levels increase during EAE in the spinal cord,\nbut AGE-modifying treatments do not inhibit EAE-induced AGE production and do not affect\ndisease progression.
Loading....