Lancet neurology
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Review
Mechanisms of glutamate toxicity in multiple sclerosis: biomarker and therapeutic opportunities.
Research advances support the idea that excessive activation of the glutamatergic pathway plays an important part in the pathophysiology of multiple sclerosis. Beyond the well established direct toxic effects on neurons, additional sites of glutamate-induced cell damage have been described, including effects in oligodendrocytes, astrocytes, endothelial cells, and immune cells. ⋯ Understanding of the mechanisms underlying glutamate toxicity in multiple sclerosis could help in the development of new approaches for diagnosis, treatment, and follow-up in patients with this debilitating disease. While several clinical trials of glutamatergic modulators have had disappointing results, our growing understanding suggests that there is reason to remain optimistic about the therapeutic potential of these drugs.