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Article
Nature Neuroscience  7, 1088 - 1095 (2004)
Published online: 26 September 2004; | doi:10.1038/nn1319

Human endogenous retrovirus glycoprotein−mediated induction of redox reactants causes oligodendrocyte death and demyelination

Joseph M Antony1, Guido van Marle1, Wycliffe Opii2, D Allan Butterfield2, François Mallet3, Voon Wee Yong1, John L Wallace4, Robert M Deacon5, Kenneth Warren6 & Christopher Power1

1  Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

2  Department of Chemistry and Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky 40506-0055, USA.

3  UMR CNRS-bioMerieux, IFR128 BioSciences Lyon-Gerland, Ecole Normale Superieure de Lyon, Lyon 69364, France.

4  Department of Pharmacology & Therapeutics, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

5  Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK.

6  Department of Medicine, University of Alberta, Edmonton, Alberta T6G 2B7, Canada.

Correspondence should be addressed to Christopher Power power@ucalgary.ca
Human endogenous retroviruses (HERVs) constitute 8% of the human genome and have been implicated in both health and disease. Increased HERV gene activity occurs in immunologically activated glia, although the consequences of HERV expression in the nervous system remain uncertain. Here, we report that the HERV-W encoded glycoprotein syncytin is upregulated in glial cells within acute demyelinating lesions of multiple sclerosis patients. Syncytin expression in astrocytes induced the release of redox reactants, which were cytotoxic to oligodendrocytes. Syncytin-mediated neuroinflammation and death of oligodendrocytes, with the ensuing neurobehavioral deficits, were prevented by the antioxidant ferulic acid in a mouse model of multiple sclerosis. Thus, syncytin's proinflammatory properties in the nervous system demonstrate a novel role for an endogenous retrovirus protein, which may be a target for therapeutic intervention.

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Nature Neuroscience
ISSN: 1097-6256
EISSN: 1546-1726
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