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Dartmouth study advances prion disease research

Hanover, NH Adding to the paradox of prion diseases, Dartmouth Medical School researchers have discovered that RNA plays a role in converting a normal prion protein into a mutant that leads to mad cow disease and other fatal brain illnesses.

Their study, reported in the Oct. 16 issue of Nature, provides important clues to understanding the role of prions, unorthodox infectious agents whose ability to transmit disease has confounded physicians and scientists. The work, by Dr. Surachai Supattapone, assistant professor of biochemistry and of medicine, opens new avenues of exploration for diagnosis and treatment of a perplexing group of neurodegenerative disorders called prion diseases.

Prions lack RNA or DNA, the nucleic acids that contain genetic information to replicate. No one knows what spurs conversion of a normal prion protein to a disease-causing counterpart. Supattapone, with coauthors Nathan Deleault and Ralf Lucassen, has discovered that RNA may be a catalyst for transformation.

"It has been well proven that nucleic acids, including RNA, are not part of the infectious agent, so it's an ironic twist that a catalyst for the reaction may be RNA," said Supattapone. He emphasized, however, that the findings are consistent with the "protein-only" hypothesis of prion diseases because the nucleic acids are in the host and are not contained in the disease spreading particle.

Prions related to infectious brain diseases such as Cruetzfeld-Jakob disease in humans, chronic wasting or scrapie in animals have long been known, but these diseases often develop over years, so research to piece together the process has moved slowly.

The discovery more than a quarter century ago that prions were proteins, devoid of nucleic acids, upended what scientists assumed not only about disease transmission, but about life itself. All mammals have a gene to make a prion protein, but the normal prion is a different shape than the infectious
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Contact: Hali Wickner
DMS.Communications@Dartmouth.edu
603-650-1492
Dartmouth Medical School
15-Oct-2003


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