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Biology and genetics of prions

Henry G Brown, MD, PhD
John M Lee, MD, PhD
Section Editors
Steven T DeKosky, MD, FAAN, FACP, FANA
Benjamin A Raby, MD, MPH
Deputy Editor
Janet L Wilterdink, MD


Prion diseases are neurodegenerative diseases that have long incubation periods and progress inexorably once clinical symptoms appear. Five human prion diseases are currently recognized: kuru, Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD also known as new variant CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI) [1-4]. Bovine spongiform encephalopathy (BSE), one of a number of prion infections affecting animals, has helped to focus more widespread public attention on these diseases with its possible link to vCJD [5,6].

These human prion diseases share certain common neuropathologic features including neuronal loss, proliferation of glial cells, absence of an inflammatory response, and the presence of small vacuoles within the neuropil which produces a spongiform appearance. Current evidence indicates that prion diseases are associated with the accumulation of an abnormal form of a host cell protein, designated the prion protein (PrP) [7].

The biology of prions will be reviewed here. The clinical manifestations, genetics, and diagnosis of prion diseases are discussed separately. (See "Diseases of the central nervous system caused by prions" and "Creutzfeldt-Jakob disease" and "Variant Creutzfeldt-Jakob disease".)


Dr. Stanley Prusiner coined the term "prion" in 1982 which he defined as a small infectious pathogen containing protein but apparently lacking nucleic acid [8]. The prion protein (PrP) is the critical component of these agents and may, in fact, be its exclusive constituent.

One of the characteristic features of prions is their resistance to a number of normal decontaminating procedures. These pathogens are resistant to processes affecting nucleic acids, such as hydrolysis or shearing [9]. However, agents that digest, denature or modify proteins do have activity against prions [7]. The prion protein purified from the brains of scrapie-infected animals (PrPSc) can be inactivated by prolonged autoclaving (at 121ºC and 15 psi for 4.5 h), or immersion in 1N NaOH (for 30 min, repeat three times), or in concentrated (>3 M) solutions of guanidine thiocyanate [10]. However, certain cautions prevail; it appears that inadequate autoclaving can establish heat resistant subpopulations which fail to diminish with a further cycle of autoclaving [11]. Stainless steel instruments also may retain infectivity even after treatment with 10 percent formaldehyde [12,13].


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Literature review current through: Sep 2016. | This topic last updated: Jul 26, 2013.
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