The role of glutamate in the pathogenesis of multiple sclerosis

Abstract

The results of recent studies indicate that the hyperactivation of the glutamatergic system plays an important role in the pathophysiology of multiple sclerosis (MS). In addition to the well-known direct toxic effect of the excessive extracellular level of the glutamate neurotransmitter on neurons, additional mechanisms of glutamate-induced cell damage have been described in the literature, including effects on oligodendrocytes, astrocytes, endothelial cells and immune cells. The study of these toxic effects will reveal the possible link between various pathological hallmarks of MS, such as axonal damage, oligodendrocyte death, demyelination, neurodegeneration, autoimmune reactions and dysfunction of blood-brain barrier. Understanding the mechanisms underlying the glutamate toxicity will contribute to the development of new therapeutic approaches for the diagnosis and treatment of patients with MS. This review focuses on the mechanisms that lead to an increase in the concentration of neurotransmitter glutamate and excitotoxicity in the context of the pathogenesis of this disease. Also the authors present the data on existing and currently developed medicines and therapeutic approaches to regulate the activity of the glutamatergic system.