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posted 14. June 2004 16:58
Science May 28, 2004
Protein Chemistry: In the Footsteps of Alchemists
Christopher M. Dobson
Summary: Both the United States and Canada recently reported their first confirmed cases of bovine spongiform encephalopathy (BSE) in cattle reared within their borders. These cases raise the specter of a spread to North America of variant Creutzfeldt-Jakob disease (vCJD), the human analog of "mad cow disease" that has afflicted Europe, particularly the United Kingdom, since the late 1980s. This devastating disease is widely believed to result from the consumption of beef contaminated with a pathogenic form of a normal cellular protein called the prion protein. Although there are grounds to hope that the severity of the European outbreak will be much less than was once feared, its ultimate magnitude is still a subject of intense speculation, as the mechanism of transmission is still unclear and the incubation period of the disease could be many decades.
Although there is much to learn about the causes of these diseases, it now appears that they are ultimately linked to a failure of the complex mechanisms that normally ensure that proteins remain in their correctly folded functional states. Such mechanisms--including the actions of folding catalysts, molecular chaperones, and degrading enzymes--normally detect misfolded or damaged proteins and either rescue or destroy them before any harm ensues. If they are not dealt with in this way, these aberrant proteins tend to self-assemble, most notoriously into the highly intractable structures known as amyloid fibrils associated with Alzheimer's disease, vCJD, type II diabetes, and many others. Indeed, such fibrils or their precursors appear to cause havoc in any tissues in which they form.