A new treatment route for bovine spongiform encephalopathy (BSE) and its human form Creutzfeldt Jakob disease (CJD) could be a step closer based on new results from scientists at the University of Leeds. The team has found that a protein called Glypican-1 plays a key role in the development of BSE. Details are published November 20 in the open-access journal PLoS Pathogens.
BSE, commonly known as mad cow disease, is known to be caused by an infectious and abnormal form of the prion protein that is present on cells within the nervous system. But scientists have been unclear as to what causes the abnormality to occur.
The new research from Leeds' Faculty of Biological Sciences provides part of the answer. The researchers have shown that the presence of Glypican-1 causes the numbers of abnormal prion proteins to rise. In experiments, when levels of Glypican-1 were reduced in infected cells, the levels of the abnormal prion reduced as well.
The discovery was a mixture of scientific detective work and luck, according to Professor of Biochemistry, Nigel Hooper.
"We were looking at how the normal prion protein functions in cells and spotted that it was interacting with something," he said. "Some lateral thinking and deduction led us to Glypican-1 and when we carried out the experiment, we found we were right."
The researchers suggest that Glypican-1 acts as a scaffold bringing the two forms of the prion protein together and that this contact causes normal prions to mutate into the infectious form. They are currently seeking further funding to investigate their hypothesis.
The findings have implications for the treatment of both BSE and the human form of the disease, CJD, according to Professor Hooper.
"Now that we know the identity of one of the key molecules in the disease process, we may in the future be able to design drugs that target this."
Although the scientists mainly conducted experiments using cells infected with prions, it is also possible that Glypican-1 is involved in other diseases of the nervous system.
"While initial experiments haven't shown any link with other neurodegenerative diseases like Alzheimer's, we're not yet completely ruling that out," said Professor Hooper.
FINANCIAL DISCLOSURE: This work was supported by the The Wellcome Trust (080229/Z/06/Z) (www.wellcome.ac.uk) and the Medical Research Council of Great Britain (G9824728) (www.mrc.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.plos.org/10.1371/journal.ppat.1000666 (link will go live upon embargo lift)
CITATION: Taylor DR, Whitehouse IJ, Hooper NM (2009) Glypican-1 Mediates Both Prion Protein Lipid Raft Association and Disease Isoform Formation. PLoS Pathog 5(11): e1000666. doi:10.1371/journal.ppat.1000666
PRESS-ONLY PDF: For a copy, please contact email@example.com
tel 0113 258 9880
mob 07980 267756
University of Leeds press office
tel 0113 343 8299
This press release refers to an upcoming article in PLoS Pathogens. The release is provided by the article authors and their institution. Any opinions expressed in these releases or articles are the personal views of the journal staff and/or article contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the releases and articles and your use of such information.
About PLoS Pathogens
PLoS Pathogens (www.plospathogens.org) publishes outstanding original articles that significantly advance the understanding of pathogens and how they interact with their host organisms. All works published in PLoS Pathogens are open access. Everything is immediately available subject only to the condition that the original authorship and source are properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org.
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.