In experiments with yeast prions reported in this week's issue of Nature, Howard Hughes Medical Institute researchers have shown how point mutations in prions -- which do not compromise their infectivity -- can nevertheless cause prions to alter the specificity of the yeast strain that they infect.
According to the researchers, their findings point the way to studies that could begin to clarify the factors that determine whether a prion specific to cattle that causes bovine spongiform encephalopathy (BSE), or mad cow disease, might become infectious to humans.
The studies also suggest a new approach for treating disorders such as Alzheimer's disease that involve aberrant protein folding, said the researchers. It might be possible to develop drugs that would influence toxic proteins that aggregate into brain-clogging plaque to fold into less toxic versions, they said.
The researchers, which included Howard Hughes Medical Institute (HHMI) investigator Jonathan Weissman, Peter Chien, HHMI predoctoral fellow Angela DePace and Sean Collins at the University of California, San Francisco, reported their findings in the August 21, 2003, issue of the journal Nature.
Unlike bacteria and viruses, prions consist only of aberrant proteins that misfold themselves into forms that, in turn, induce their normal counterparts to misfold. In mammalian prion infections, these abnormal, insoluble proteins trigger protein clumping that can kill brain cells. In humans, clumping causes fatal brain-destroying human diseases such as Creutzfeldt-Jakob disease and kuru, and in animals it causes BSE and scrapie.