The Role of Glutamate in the Pathogenesis of Multiple Sclerosis

Abstract

Results from studies in recent years have provided evidence that hyperactivation of the glutamatergic system plays an important role in the pathophysiology of multiple sclerosis (MS). Apart from the well known immediate toxic effects of the neurotransmitter glutamate on neurons, additional mechanisms of glutamate-induced cell injury have been described, these including actions of oligodendrocytes, astrocytes, endothelial cells, and immune cells. These toxic effects may open up a link between the various pathological components of MS, such as axon damage, oligodendrocyte death, demyelination, autoimmune reactions, and dysfunction of the blood-brain barrier. Understanding the mechanisms underlying glutamate toxicity in MS may be promoted by the development of new approaches to the diagnosis, treatment, and management of patients with MS. This review presents reports on the mechanisms leading to increases in the concentration of the neurotransmitter glutamate and excitotoxicity in the context of the pathogenesis of the disease. We also present data on drugs and therapeutic approaches, both current and under development, helping to regulate the operation of the glutamatergic system.