prion

Small, infectious proteinaceous particle, of nonnucleic acid composition because of its resistance to nucleases; the causative agent, either on a sporadic, genetic, or infectious basis, of six neurodegenerative diseases in animals, and four in humans; the latter include the spongiform encephalopathies of kuru, Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia. The gene encoding for the PrP is found on chromosome 20. SYN: p. protein. [proteinaceous infectious particle] Stanley B. Prusiner received the Nobel Prize in Physiology or Medicine in 1997 for his discovery of prions. Prusiner began his research in 1972 to identify the infectious agent of Creutzfeldt-Jakob disease. In 1982 he and his colleagues isolated a protein that was capable of transmitting infection but, unlike all other known pathogens, contained neither DNA nor RNA. Prusiner's term for this protein, p., was derived from the phrase proteinaceous infectious particle. A gene encoding this protein has been found in all animals tested, including humans. The p. protein can occur in either of 2 structural conformations, one that is normal (but of unknown function), designated PrPc, and one that results in disease, called PrPSc. The normal p. protein is a component of lymphocytes and other cells and is particularly abundant on the cell membranes of CNS neurons. The PrPSc p. protein is extremely stable and is resistant to proteolysis, organic solvents, and high temperatures. Once produced or acquired by a suitable host, it can initiate a chain reaction whereby normal PrPc protein is converted into the more stable PrPSc form. After a long, asymptomatic incubation period, the disease-causing PrPSc accumulates to reach neurotoxic levels. Symptoms of p. diseases vary with the parts of the brain affected. All known p. diseases lead to the death of those affected. P. diseases are called spongiform encephalopathies because of the histologic appearance of affected cerebral cortex and cerebellum, which display large vacuoles. Probably most mammalian species develop these diseases. Prions are not living, are smaller than viruses, and do not elicit an immune response in either their normal or disease-causing form. P. diseases besides Creutzfeldt-Jakob disease include kuru (once prevalent among the Fore people of New Guinea, who practiced ritual cannibalism), bovine spongiform encephalopathy (BSE, mad cow disease), and scrapie, a disease of sheep. A new variant of CJD may have arisen through transmission of prions to human beings from cattle infected with BSE. P. diseases are unique in being both infectious and hereditary. Hereditary forms are due to transmitted mutations in the p. gene, located on chromosome 20 in human beings. Gertsmann-Sträussler-Scheinker (GSS) disease is a hereditary dementia resulting from a mutation in this gene. Approximately 50 families with GSS mutations have been identified. About 10–15% of cases of CJD are caused by inherited mutations in the p. protein gene. Strains of mice from which this gene has been abolished are immune to p.-caused disease. See Creutzfeldt-Jakob disease, bovine spongiform encephalopathy.

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pri·on 'prē-.än n a protein particle that lacks nucleic acid and has been implicated as the cause of various neurodegenerative diseases (as scrapie, Creutzfeldt-Jakob disease, and bovine spongiform encephalopathy)

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n.

an abnormal form of a constituent protein (PrP) of brain cells. Prions are produced by mutations in the gene that codes for PrP and are very stable: they are not removed by the normal cellular processes of degradation and are resistant to radiation. They are believed to interact with normal PrP in such a way as to convert it to the abnormal form, which accumulates in the brain. Prions are now widely accepted as being the causal agents of a range of serious diseases including Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, and kuru, all of which are spongiform encephalopathy. Different mutations in the PrP gene are believed to be responsible for the different forms of these so-called prion diseases.

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pri·on (priґon) (preґon) [protein infectious agent] any of several protease-resistant, insoluble, transmissible isoforms of the 27–30 kD core of prion protein that cause a group of progressive neurodegenerative diseases (prion diseases). Prions have a pleated sheet conformation rather than the α helix structure that is normal for prion protein, lack detectable nucleic acid, and do not elicit an immune response.