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Lab experiments reveal potential therapeutic target for degenerative brain diseases

Laboratory experiments on prion diseases -- degenerative brain illnesses such as Kuru and Crutzfeldt-Jakob disease in humans, scrapie in sheep, and the so-called "mad cow disease" -- have yielded a surprising clue to what may be a way to prevent these diseases. In the August issue of the Journal of Virology, scientists from the National Institute of Allergy and Infectious Diseases (NIAID) and their colleagues in France and the United Kingdom report that a small piece of the prion protein (PrP) prevents the larger molecule from folding incorrectly. Since abnormal folding is associated with prion disease, blocking the ability of the prion protein to assume an abnormal shape could be key to blocking progression to disease.

"Prion disease pathology requires misfolded prion proteins," comments NIAID Director Anthony S. Fauci, M.D. "This study demonstrates that, at least in a test tube, a section of the prion protein can be used to maintain proper shape. This insight opens the possibility of preventing prion diseases."

Prion diseases, officially called transmissible spongiform encephalopathies (TSEs), are uniformly fatal illnesses that cause infected brains to look like Swiss cheese at autopsy. These diseases gained widespread notoriety in the mid-1990s when 34 people in the United Kingdom developed a progressive neurological breakdown leading to death. The most commonly believed source of disease for humans is meat from "mad cows" afflicted with bovine spongiform encephalopathy (BSE).

Despite recent indications that BSE crosses from cows to humans, these infections tend to stay in the animal species where they originate. Scientists at NIAID's Rocky Mountain Laboratories (RML) in Montana and their colleagues, for example, recently demonstrated that abnormal PrP from a mouse cannot convert normally folded PrP from a hamster. However, these investigators recognized that the PrP from the mouse, hamster, and a second strain of mouse all shared t
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