Synthetic Prion Causes Neurological Disease in Mice
Scientists have produced a prion protein that can trigger the development of a neurological disorder in mice that is similar to "mad cow" disease, according to a new study supported by the National Institute on Aging (NIA), a part of the National Institutes of Health. The findings demonstrate that prions, an unusual class of infectious proteins, can make copies of themselves without the presence of viral DNA or RNA, damage brain tissue, and cause neurological diseases.
The work by Nobel Laureate Stanley B. Prusiner, M.D., and colleagues at the
University of California, San Francisco, and Heinrich-Heine Universitat
in Germany, appears in the July 30, 2004, issue of Science.
For the study, Dr. Prusiner and his colleagues produced prion protein
fragments in bacteria, folded them into larger protein structures
called amyloid fibrils, and then injected them into the brains of
susceptible mice. The mice began exhibiting symptoms of disease
in their central nervous systems between 380 and 660 days after
they were given the synthetic prion proteins. The amyloid form of
the prion protein, which is thought to cause prion disease, was
also found in the brains of the diseased mice. The researchers then
administered brain extracts from these animals to another group
of mice, which subsequently developed similar symptoms 90 to 150
days later. The disorder seems to be distinct from that caused by
other known strains of prions, suggesting that the synthetic prion
didn't merely activate a pre-existing prion in these mice and that
the synthesized prion protein itself is sufficient to make infectious
and disease-causing prions.
Prusiner received the 1997 Nobel Prize in physiology or medicine for his discovery of prions. Unlike viruses, bacteria, fungi and parasites, prions contain no DNA or RNA. Instead, they are a type of protein normally found within cells in humans and other organisms. In some cases, the structure of prions can change into a disease-causing form. These abnormal proteins appear to convert other, normal prions to the abnormal shape. Many scientists now believe this conversion process leads to several dementing diseases in humans, including Creutzfeldt-Jakob disease. Similar diseases in animals include bovine spongiform encephalopathy ("mad cow" disease) in cattle and scrapie in sheep. Abnormal, misfolded proteins contribute to other age-related neurological diseases such as Alzheimer's and Parkinson's diseases, and so these new findings may provide insights into the cause and possible prevention of other brain disorders.
EDS: Andrew Monjan, Ph.D., of the NIA's Neuroscience and Neuropsychology
of Aging Program is available to discuss this finding. For an interview,
please phone (301) 496-1752.