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Researchers make major gain in understanding how prions jump species

CLEVELAND Researchers at Case Western Reserve University School of Medicine have taken a major step towards understanding how abnormal prion proteins, the suspected cause of mad cow and related diseases, change shape to jump from one animal species to another. In test tube experiments, they were able to make human prion proteins exhibit characteristics of mouse prions or hamster prions through the substitution of either one or two amino acids. Furthermore, they describe how prions may overcome natural transmissibility barriers between two species of mammals. This may happen if prion proteins from one of these two species have been exposed to abnormal prions from a third species.

The Case team's findings are reported in the April 9 issue of Molecular Cell. The senior author of the study is Witold Surewicz, Ph.D., professor of physiology and biophysics at Case. It is co-authored by David Vanik, Ph.D., and Krystyna Surewicz, Ph.D.

The new study demonstrates that fundamental aspects of prion propagation in mammals, including the species barrier and strain diversity, can be reproduced in a test tube using a highly purified protein, a finding that provides a strong support for the hypothesis that mad cow disease and related disorders are caused by prion proteins only.

Prion diseases, also known as transmissible spongiform encephalopathies, are a group of infectious neurodegenerative disorders that include Creuzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (mad cow disease) in cattle, and chronic wasting disease in deer and elk. It is generally believed that the infectious agent responsible for these fatal diseases is not a virus, but an abnormally shaped form of the prion protein. This highly unusual pathogen is believed to propagate by acting as a template that binds to normal prion protein and forces it to change shape into an abnormal, pathogenic form.

"While abnormally shaped proteins can readily act as templates
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Contact: George Stamatis
George.Stamatis@case.edu
216-368-3635
Case Western Reserve University
8-Apr-2004


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