PMID:15452578

Citation	Antony, JM, van Marle, G, Opii, W, Butterfield, DA, Mallet, F, Yong, VW, Wallace, JL, Deacon, RM, Warren, K and Power, C (2004) Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination. Nat. Neurosci. 7:1088-95
Abstract	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.
Links	PubMed Online version:10.1038/nn1319
Keywords	Adult; Aged; Animals; Antioxidants/pharmacology; Antioxidants/therapeutic use; Astrocytes/immunology; Astrocytes/metabolism; Astrocytes/virology; Cell Death/immunology; Cell Line; Coumaric Acids/pharmacology; Coumaric Acids/therapeutic use; Disease Models, Animal; Encephalitis/drug therapy; Encephalitis/immunology; Encephalitis/virology; Endogenous Retroviruses/genetics; Endogenous Retroviruses/immunology; Endogenous Retroviruses/metabolism; Gene Products, env/genetics; Gene Products, env/metabolism; Humans; Mice; Middle Aged; Multiple Sclerosis/drug therapy; Multiple Sclerosis/immunology; Multiple Sclerosis/virology; Myelin Sheath/metabolism; Oligodendroglia/immunology; Oligodendroglia/metabolism; Oxidation-Reduction; Pregnancy Proteins/genetics; Pregnancy Proteins/metabolism; RNA, Messenger/metabolism; Rats; Reactive Oxygen Species/antagonists & inhibitors; Reactive Oxygen Species/metabolism; Recombinant Fusion Proteins/pharmacology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:ENW1		GO:0001948: glycoprotein binding	ECO:0000314:		F		Figure 3	complete CACAO 9436

References

See Help:References for how to manage references in GONUTS.