New prion protein may offer insight into mad cow disease

"Our team has defined a second prion protein called 'Shadoo,' that exists in addition to the well-known prion protein called 'PrP'," said Westaway, a neurology professor and director of the Centre for Prions and Protein Folding Diseases at the University of Alberta.

"For decades we believed PrP was a unique nerve protein that folded into an abnormal shape and caused prion disease - end of story. This view is no longer accurate," Westaway added.

Westaway joined the U of A after leaving the University of Toronto a year ago. The study was conducted jointly by the U of A, U of T, Case Western Reserve University (Ohio) and the McLaughlin Research Institute in Montana. The research is published in the EMBO Journal and represents a culmination of work initiated in 1999.

"It's taken years," Westaway said of the search for a new protein.

"A second prion protein had been inferred by other research, based on indirect studies and the examination of DNA sequences," said lead author Joel Watts, a graduate student at the U of T Centre for Research in Neurodegenerative Diseases. "But we not only demonstrate that this theoretical protein really exists and shares several properties with healthy PrP; we have also defined an unexpected alteration in prion infections."

"As the PrP molecule alters shape and accumulates in a prion-affected brain, the Shadoo protein seems to disappear," Watts added. Because proteins in a living cell are the molecules "that do the work, this is likely to be significant," he said.

Proteins are built up from amino acid building blocks, like beads on a string. However, these strings can fold up into highly complex three-dimensional shapes, called "conformations." Proteins carry out the important activities of living cells. For example, these can serve a structural role as scaffolds, they can act as molecular motors to move other molecules, they can sense the environment near the cell and they can catalyze chemical reactions.

Prions are proteinaceous infectious pathogens that cause diseases like BSE (mad cow disease) and Creutzfeldt-Jakob disease.

"Many facets of a prion disease like BSE are puzzling," Westaway said. "The puzzles include the cause of death of brain cells, the function of normal prion proteins, and the rules governing emergence and spread of prions from animal to animal. We believe the Shadoo protein can give us a fresh purchase on these important questions."

Source: University of Alberta

New prion protein may offer insight into mad cow disease
Scientists have discovered a new protein that may offer fresh insights into brain function in mad cow disease. “Our team has defined a second prion protein called ‘Shadoo’, that exists in addition to the well-known prion protein called ‘PrP’ ” said Professor David Westaway, director of the Centre for Prions and Protein Folding Diseases at the University of Alberta.
Tracking Down the Cause of Mad Cow Disease
(PhysOrg.com) -- The cause of diseases such as BSE in cattle and Creutzfeld–Jakob disease in humans is a prion protein. This protein attaches to cell membranes by way of an anchor made of sugar and lipid components (a glycosylphosphatidylinositol, GPI) anchor. The anchoring of the prions seems to have a strong influence on the transformation of the normal form of the protein into its pathogenic form, which causes scrapie and mad cow disease.
Is there more to prion protein than mad cow disease?
Prion protein, a form of protein that triggers BSE, is associated with other brain diseases in cattle, raising the possibility of a significant increase in the range of prion disease. Publishing their findings in the open access journal BMC Veterinary Research, scientists have detected changes in the production and accumulation of the prion protein in the brains of cattle with a rare neurodegenerative disorder.
Protective pathway in stressed cells not so helpful when it comes to prions
Scientists at the National Institutes of Health (NIH) have discovered that an important cellular quality control mechanism may actually be toxic to some brain cells during prion infection. The research, published by Cell Press in the September 16th issue of the journal Developmental Cell, proposes a new general mechanism of cellular dysfunction that can contribute to the devastating and widespread neuronal death characteristic of slowly progressing neurodegenerative diseases.
Newresearch shows mad cow disease also caused by genetic mutation
New findings about the causes of mad cow disease show that sometimes it may be genetic. "We now know it's also in the genes of cattle," said Juergen A. Richt, Regents Distinguished Professor of Diagnostic Medicine and Pathobiology at Kansas State University's College of Veterinary Medicine.
Changes in urine could lead to BSE test for live animals
Researchers have demonstrated that protein levels in urine samples can indicate both the presence and progress of Bovine Spongiform Encephalopathy (BSE) disease in cattle. Publishing their findings in BioMed Central's open access journal Proteome Science, the scientists hope that their discovery might lead to the development of a urine-based test that could prevent the precautionary slaughter of many animals as now occurs when the disease is detected.
Infectious, test tube-produced prions can jump the 'species barrier'
Researchers have shown that they can create entirely new strains of infectious proteins known as prions in the laboratory by simply mixing infectious prions from one species with the normal prion proteins of another species. The findings are reported in the September 5th issue of the journal Cell.
A novel approach in the molecular differentiation of prion strains
A team from the French Food Safety Agency, Lyon, France, has identified a prion protein characteristic that is unique to some natural but unusual sheep scrapie cases. This finding, reported August 29th in the open-access journal PLoS Pathogens, may provide a novel method by which to study prion diversity and their possible changes during cross-species transmission.

New prion protein may offer insight into mad cow disease

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