Prion Diseases and the BSE Crisis

[Autoclave.Guru]

Note: Due to the interest in Dr. Prusiner's article, Science is offering its readers free access to the associated News item: Prusiner Recognized for Once-Heretical Prion Theory, by Gretchen Vogel.

Prion Diseases and the BSE Crisis

Stanley B. Prusiner
Bovine spongiform encephalopathy (BSE) and human Creutzfeldt-Jakob disease (CJD) are among the most notable central nervoussystem degenerative disorders caused by prions. CJD may presentas a sporadic, genetic, or infectious illness. Prions are transmissibleparticles that are devoid of nucleic acid and seem to be composedexclusively of a modified protein (PrP^Sc). The normal, cellular prion protein (PrP^C) is converted into PrP^Sc through a posttranslational process during which it acquiresa high -sheet content. It is thought that BSE is a result ofcannibalism in which faulty industrial practices produced prion-contaminatedfeed for cattle. There is now considerable concern that bovineprions may have been passed to humans, resulting in a new formof CJD.
Department of Neurology (address for correspondence) and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
During the past two decades, a previously unknown mechanism of disease has been described in humans and animals. Several fatalillnesses, often referred to as the prion diseases and includingscrapie of sheep, BSE, and CJD of humans, are caused by the accumulationof a posttranslationally modified cellular protein. Indeed, thehallmark of all prion diseases--whether sporadic, dominantly inherited,or acquired by infection--is that they involve the aberrant metabolismand resulting accumulation of the prion protein (Table 1) (1,2). The conversion of PrP^C (the normal cellular protein) into PrP^Sc (the abnormal disease-causing isoform) involves a conformationchange whereby the -helical content diminishes and the amountof sheet increases (3). This structural transition is accompaniedby profound changes in the properties of the protein: PrP^C is soluble in nondenaturing detergents, whereas PrP^Sc is not (4); and PrP^C is readily digested by proteases, whereas PrP^Sc is partially resistant (5