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Journal of Translational Neuroscience(转化神经科学电子杂志)

ISSN 2096-0689

CN 11-9363/R

Journal of Translational Neuroscience    2016, Vol. 1 Issue (2) : 49-55    https://doi.org/10-3868/j.issn.2096-0689.2016.02.004
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Is autoimmunity in multiple sclerosis secondary to neurodegeneration?
Albert HC Wong, Fang Liu
1.Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON,M5T 1R8,Canada 2.Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, M5T 1R8, Canada
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Abstract Abstract Multiple sclerosis (MS) is characterized by neurological symptoms that are separated in time and space, which correlate with demyelination and white matter lesions. The conventional pathophysiological model is that an autoimmune reaction against the myelinated nerve sheath results in demyelination, accompanied by axon damage and the death of oligodendrocytes that produce myelin. There is no cure for MS, but current treatments are primarily aimed at suppressing the autoimmune reaction, with the goal of reducing demyelination. These treatments have limited efficacy and developing better treatments for MS remains an important goal. Here we argue that the autoimmune reaction may be secondary to neurodegeneration or neurotoxicity, and that protecting neurons from glutamate-mediated toxicity may be a better therapeutic strategy than targeting the immune system. We have recently demonstrated that a protein-protein interaction between the GluR2 subunit of the AMPA (α-Amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid) glutamate receptor and GAPDH (Glyceraldehyde 3-phosphate dehydrogenase) is elevated in human MS plaques and in an animal model of MS. Disrupting this interaction in a rodent model restores neurological function, preserves myelin, and protects neurons, oligodendrocytes and axons. The peptide we created to block the GluR2-GAPDH interaction also reduces immune system activation, suggesting that autoimmunity is not necessarily the primary etiology in MS. The GluR2-GAPDH interaction may promote cell death via increased calcium influx through non-GluR2-containing AMPA receptors, or through the p53 and Siah1 cell death pathways.
Keywords multiple sclerosis (MS), autoimmunity,GluR2, GAPDH     
Issue Date: 18 December 2016
 Cite this article:   
Albert HC Wong, Fang Liu. Is autoimmunity in multiple sclerosis secondary to neurodegeneration?[J]. Journal of Translational Neuroscience,2016, 1(2): 49-55.
 URL:  
https://academic.hep.com.cn/jtn/EN/10-3868/j.issn.2096-0689.2016.02.004
https://academic.hep.com.cn/jtn/EN/Y2016/V1/I2/49
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