Adopted protein might be MS culprit
Nathan Seppa
When the fatty sheaths that insulate nerve fibers in the brain become damaged, the result is multiple sclerosis (MS). But the cause of this destruction has long baffled researchers. One group now reports that a protein called syncytin might be at fault.
Christopher Power of the University of Calgary in Alberta and his colleagues report in the October Nature Neuroscience that brain tissue collected from MS patients at autopsies harbors about three times as much syncytin as does postmortem brain tissue from people without MS.
To see what role syncytin might play in MS, the researchers cultured human brain cells in lab dishes. Using a genetically engineered virus that promotes syncytin production, the scientists induced cells called astrocytes to crank out the protein. The cells then released inflammatory proteins and damaging oxidizing compounds called free radicals. This combination killed oligodendrocytes, brain cells that maintain the myelin sheaths that insulate nerve fibers.
When the scientists injected the syncytin-promoting virus into the brains of live mice, the viruses invaded astrocytes and caused these cells to produce large amounts of the protein. Within 2 weeks, the mice developed muscle-coordination problems reminiscent of MS symptoms. Mice given an antioxidant recovered.
The gene for syncytin is an oddity. Scientists hypothesize that it was captured from retroviruses that invaded the human genome roughly 1 million years ago (SN: 5/13/00, p. 318: Available to subscribers at http://www.sciencenews.org/articles/20000513/bob9.asp). The gene is normally quiescent, except when playing a role in placental development, says Mark P. Mattson, a neuroscientist at the National Institute of Aging in Baltimore.
"It's not clear why the gene for syncytin is activated in astrocytes of MS patients," he says. Even so, the finding could open up a new strategy for developing treatments for MS.
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References:
Antony, J.M. … and C. Power. 2004. Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination. Nature Neuroscience 7(October):1088–1095. Abstract available at http://dx.doi.org/10.1038/nn1319.
Further Readings:
Blond, J.-L. … F. Mallet, et al. 2000. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. Journal of Virology 74(April):3321–3329. Available at http://jvi.asm.org/cgi/content/full/74/7/3321.
Blond, J.-L., et al. 1999. Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family. Journal of Virology 73(February):1175–1185. Available at http://jvi.asm.org/cgi/content/full/73/2/1175.
Hughes, J.F., and J.M. Coffin. 2001. Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nature Genetics 29(December):487–489. Abstract available at http://dx.doi.org/10.1038/ng775.
Mattson, M.P., and D.D. Taub. 2004. Ancient viral protein enrages astrocytes in multiple sclerosis. Nature Neuroscience 7(October):1021–1023. Abstract available at http://dx.doi.org/10.1038/nn1004-1021.
Mi, S., et al. 2000. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403(Feb. 17):785–789. Abstract available at http://dx.doi.org/10.1038/35001608.
Travis, J. 2000. Placental puzzle. Science News 157(May 13):318–319. Available to subscribers at http://www.sciencenews.org/articles/20000513/bob9.asp.
Sources:
Mark P. Mattson
Laboratory of Neurosciences
National Institute on Aging Intramural Research Program
5600 Nathan Shock Drive
Baltimore, MD 21224
Christopher Power
Department of Clinical Neurosciences
University of Calgary
Calgary, AB T2N 4N1
Canada
From Science News, Volume 166, No. 15, October 9, 2004, p. 237.
