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 the same core region. This shared section of the
PrP inhibited conversion of normal PrP to abnormal PrP in both rodent
"In our experiments, we showed that adding a peptide derived from the core
of the prion protein dramatically reduced the generation of abnormal PrP
associated with prion disease," explains lead author Joelle Chabry, Ph.D.,
from the Centre National de la Recherche Scientifique (CNRS) in France.
"Because the core region is very conserved in most species of prion
protein," remarks senior author and RML researcher Bruce Chesebro, M.D.,
"this peptide may inhibit the prion protein conversions in a wide variety of
Although the mechanism of inhibition is not known, the importance of the
reaction lies in its potential application to actual disease. Using
scrapie-infected mouse cells, the investigators blocked the production of
new, abnormal PrP by incubating the cells with the core peptide. Such an
approach opens possibilities for therapy in animals.
Protein shape changes associated with prion diseases protect the abnormal
prion protein from breakdown by the body. The resistant proteins build up
and form insoluble plaques leading to neurological problems. These effects
may not appear until years or even decades later, and have been a major
stumbling block for researchers. Other diseases characterized by
development of plaques and that may be related to prion diseases include
Alzheimers and Parkinson's disease.
"No one would have suspected that a piece of the prion protein itself might
prevent further disease," says Dr. Chesebro. "Although the research is not
at the point of preventing disease in humans or, for that matter, in cows,
we're excited that this therapeutic approach might prove beneficial."
NIAID is a component of the National Institutes of Health (NIH). NIAID
conducts and supports research to prevent, diagnose and treat illnesses such
as HIV disease and other sexually transmitted diseases, tuberculosis,
malaria, asthma and allergies. NIH is an agency of the U.S. Department of
Health and Human Services.
Press releases, fact sheets and other materials are available on the NIAID
Web site at www.niaid.nih.gov.