Prion Support

NEUROSCIENCE

Proof that misformed proteins known as prions are the sole cause of some fatal mammalian brain diseases--mad cow disease, scrapie, and Creutzfeld-Jakob disease--has been claimed by a group of researchers at the University of Texas Medical Branch in Galveston (Cell 2005, 121, 195).

"The evidence in favor of the prion hypothesis was strong, but the final proof was still missing," says Claudio Soto, a neurology professor at the UT Medical Branch. "Now we have supplied this proof."

Stanley B. Prusiner won the Nobel Prize for Physiology or Medicine in 1997 for the hypothesis that prions cause these fatal brain disorders. The proposed disease mechanism has remained controversial, however.

Soto's group bases its claim on the results of an experiment involving hamsters. The researchers homogenized brains from animals infected with scrapie, diluted the mixture, and added it to brain homogenate from healthy hamsters.

The scrapie prion proteins (PrP^Sc) from the diseased brains induced normal prion proteins from the healthy brains to misfold, converting their native -helical structures into β-sheets. The misfolded prions formed clumps, which were broken apart with sound waves. The smaller clumps induced further misfolding.

After several cycles of misfolding, clumping, and clump breaking, the original PrP^Sc was so diluted that essentially none of it was present in the final samples. The researchers injected the resulting prions into the brains of healthy hamsters, which developed scrapie symptoms and died.

Neuropathologists at Case Western Reserve University applaud the work but say it doesn't offer ultimate proof.

"Although the study makes significant progress toward proving the prion hypothesis, it still falls a bit short of achieving this goal," write Wen-Quan Zou and Pierluigi Gambetti in a commentary. "For example, the possibility remains that RNA or other molecules present in the original brain preparation might be amplified along with PrP^Sc and might play a critical role in conferring infectivity ... to the new PrP^Sc."