title: Mechanisms of glutamate toxicity in multiple sclerosis: biomarker and therapeutic opportunities.
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.
authors: INSERM U919, University of Caen Normandy, Caen, France.
authors: Richard
authors: R
authors: Macrez
authors: Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors: Peter K
authors: PK
authors: Stys
authors: INSERM U919, University of Caen Normandy, Caen, France.
authors: Denis
authors: D
authors: Vivien
authors: Scintillon Institute San Diego, CA, USA; Scripps Research Institute, La Jolla, CA, USA; School of Mecicine, University of California, San Diego, CA, USA.
authors: Stuart A
authors: SA
authors: Lipton
authors: INSERM U919, University of Caen Normandy, Caen, France. Electronic address: docagne@cyceron.fr.
authors: Fabian
authors: F
authors: Docagne
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid