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Brown team finds crucial protein role in deadly prion spread

PROVIDENCE, R.I. [Brown University] -- A single protein plays a major role in deadly prion diseases by smashing up clusters of these infectious proteins, creating the "seeds" that allow fatal brain illnesses to quickly spread, new Brown University research shows.

The findings are exciting, researchers say, because they might reveal a way to control the spread of prions through drug intervention. If a drug could be made that inhibits this fragmentation process, it could substantially slow the spread of prions, which cause mad cow disease and scrapie in animals and, in rare cases, Creutzfeldt-Jacob disease and kuru in humans.

Because similar protein replication occurs in Alzheimer's and Parkinson's diseases, such a drug could also slow progression of these diseases as well.

"The protein fragmentation we studied has a big impact on how fast prion diseases spread and may also play a role in the accumulation of toxic proteins in neurodegenerative diseases like Parkinson's," said Tricia Serio, an assistant professor in Brown's Department of Molecular Biology, Cell Biology and Biochemistry and lead researcher on the project.

The findings from Serio and her team, which appear online in PLoS Biology, build on their groundbreaking work published in Nature in 2005. That research showed that prions strange, self-replicating proteins that cause fatal brain diseases convert healthy protein into abnormal protein through an ultrafast process.

This good-gone-bad conversion is one way that prions multiply and spread disease. But scientists believe that there is another crucial step in this propagation process fragmentation of existing prion complexes. Once converted, the thinking goes, clusters of "bad" or infectious protein are smashed into smaller bits, a process that creates "seeds" so that prions multiply more quickly in the body. Hsp104, a molecule known to be required for prion replication, could function as this protein "
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Contact: Wendy Lawton
Wendy_Lawton@brown.edu
401-863-1862
Brown University
23-Jan-2007


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