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.
Highlights
Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS) [1]
We observed significantly increased levels of free MG-H1 in the plasma of mice subjected to EAE compared to healthy controls (Table 1)
Our study shows that levels of dicarbonyls and advanced glycation endproducts (AGEs) are significantly increased in the CNS of mice subjected to EAE
Summary
Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS) [1]. 2.5 million people are diagnosed with MS; mainly young adults as the disease manifests between 20 and 40 years of age. These patients have a variety of symptoms including muscle weakness, paresthesias, ataxia, and visual disturbances, depending on the brain regions attacked by the immune system [2]. There is consensus that MS is triggered by environmental factors in genetically susceptible hosts This leads to an immune response targeted at the myelin sheaths surrounding the axons. Whether this immune response is initiated inside or outside of the CNS is, to date, still unclear. The autoimmune response leads to neuroinflammation and demyelination, primarily in the spinal cord [7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
