University Of California-San Francisco Researchers Report Test That Detects Prion Diseases, Illuminates Novel,,Findings About Infectious Prions

They plotted the results as a function of the concentration of PrPSc for each strain. And their findings were dramatic. Like seemingly insignificant holes cut in paper can create the image of a snowflake, the points on the graph revealed detail about the proteins' unique properties that the molecular biologists couldn't see on their own: specifically, that each of the eight different strains of infectious prions had unique shapes.

Researchers have known that prion diseases, even within species, vary in length of incubation, topology of prion accumulation and distribution of accumulated protein deposits in the brain. But while they have suspected that these variations, or strains, were represented by different protein shapes, they have never had direct evidence. Moreover, it has long been believed that a protein has only a single conformation, as determined by its amino acid sequence, and all eight strains did represent a single molecular sequence.

"We know that PrPC and PrPSc have very distinct shapes. What has become clear is that while all of the strains contain a common molecular sequence, each protein strain has a distinct shape," said Fred E. Cohen, MD, PhD, a professor of pharmacology and medicine at UCSF and a co-senior author of the study.

The assay also revealed that PrPSc protein contains a protease-sensitive fraction, which surprised the researchers. "We always thought PrPSc was strictly protease resistant," said Stanley B. Prusiner, MD, a professor of neurology, biochemistry and biophysics at UCSF, the winner of the 1997 Nobel Prize in Physiology or Medicine, and the other senior author of the study.

In an effort to tease out the component of prion protein that might actually confer the most crucial distinction in strains--the time it takes for the disease to develop--the researchers plotted the protease-sensitive component of the PrPSc versus incubation time and were struck by what Safar called 'a gorgeo

Contact: Jennifer O'Brien
(415) 476-2557
University of California - San Francisco

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