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Lancet Neurol. 2016 Sep;15(10):1089-102. doi: 10.1016/S1474-4422(16)30165-X. Epub 2016 Aug 8.

Mechanisms of glutamate toxicity in multiple sclerosis: biomarker and therapeutic opportunities.

Author information

1
INSERM U919, University of Caen Normandy, Caen, France.
2
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
3
Scintillon Institute San Diego, CA, USA; Scripps Research Institute, La Jolla, CA, USA; School of Mecicine, University of California, San Diego, CA, USA.
4
INSERM U919, University of Caen Normandy, Caen, France. Electronic address: docagne@cyceron.fr.

Abstract

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. Such toxic effects could provide a link between various pathological aspects of multiple sclerosis, such as axonal damage, oligodendrocyte cell death, demyelination, autoimmunity, and blood-brain barrier dysfunction. 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.

PMID:
27571160
DOI:
10.1016/S1474-4422(16)30165-X
[Indexed for MEDLINE]

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