Prions
A prion, short for "proteinaceous infectious articles," is a protein capable of causing both inheritable and communicable disease by inducing benign proteins to change their shape. This shape change renders the protein infectious. When the notion of prions was first suggested in the 1970s by Stanley Prusiner, a neurologist at the University of California at San Francisco, it was heretical. Dogma held that the conveyers of transmissible diseases required genetic material, composed of nucleic acid (DNA or RNA), in order to establish an infection in a host. Time and the accumulation of experimental evidence proved Prusiner correct. For his discovery of prions and the elucidation of their infectious mechanism, Prusiner received the 1997 Nobel Prize in medicine.
The known prion diseases, all fatal, are known as spongiform encephalopathies. They frequently cause the brain to become riddled with holes, and rod-shaped particles clumped together in large arrays are evident. The diseases are widespread in animals and develop slowly over the course of years, even decades in humans. The most common form is scrapie, found in sheep and goats. Afflicted animals lose coordination and become incapacitated, unable to stand. Other prion diseases of animals are called transmissible mink encephalopathy, chronic wasting disease of mule deer and elk, feline spongiform encephalopathy and bovine spongiform encephalopathy (also referred to as mad cow disease). The list of known human prion diseases is growing, and includes Kuru, Creutzfeldt-Jacob disease, Gerstmann-Straussler-Scheinker disease and fatal familial insomnia. Unproven, but suspected human diseases include Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis ("Lou Gehrig's disease").
Research by Prusiner and others in the 1970s and 1980s demonstrated that prions produced a single gene product, a protein called PrP (for prion protein). In the late 1980s, Prusiner and colleagues showed that PrP was present in the brains of people afflicted with Gerstmann-Straussler-Scheinker syndrome, a rare spongiform encephalopathy. The protein was also present in healthy individuals, but differed from the other Prp by a single amino acid-- a point mutation. Analysis of a large number of patients with the syndrome established a genetic linkage between the mutation and the disease. Further research found scrapie to result from a similar mutation.
The mechanism of prion's is not fully understood. It is known that the disease is caused by a shape change of PrP. The mutated PrP adopts a sheet-like structure, whereas the normal form is more helical in shape. Yet, mutated and normal forms of PrP have been shown to have the same amino acid sequences. Somehow, the accumulation of the sheet-like forms in the brain causes damage. Preventing the conversion to the sheet format might be a useful therapy or preventative step in prion diseases.
The tranmissibility of prion from one species to another is controversial and still unresolved. PrPs from different species differ in their amino acid sequences. The differences can be slight to considerable; cows and human PrPs are very divergent, differing by over 30 amino acids. Prusiner and others are pursuing the notion that species barrier may be breached if the PrPs are very similar. Nonetheless, the development of Creutzfeld-Jacob disease in several farmers whose herds developed mad cow disease might be noteworthy.
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