The researchers reported their findings in the October 2004 issue of the Public Library of Science Biology. They were led by Howard Hughes Medical Institute investigator Jonathan S. Weissman at the University of California, San Francisco. HHMI investigator Ronald D. Vale, also of UCSF, was a co-author of the article.
Working in yeast, Weissman and his colleagues investigated the mechanism by which a prion protein assembles individual polypeptides into long amyloid fibers. These fibers are similar to the amyloid plaques that clog the brains of patients with Alzheimer's or Parkinson's disease.
Unlike bacteria and viruses, prions consist only of aberrant proteins that misfold into forms that, in turn, induce normal proteins to misfold. In mammalian prion infections, these abnormal, insoluble proteins trigger protein clumping, producing a plaque that can kill brain cells. In humans, clumping causes fatal brain-destroying diseases such as Creutzfeldt-Jakob disease and kuru; in animals it causes bovine spongiform encephalopathy (mad cow disease) and scrapie.
In the yeast cells Weissman and his colleagues used as research models, however, the insoluble prion merely alters a cell's metabolism. Besides offering a model for studying prions, the yeast system also provides an excellent model for the growth and aggregation of amyloid protein, said Weissman. Studying this process could have important implications for understanding amyloid diseases, h
Contact: Jennifer Michalowski
Howard Hughes Medical Institute