US neurologist who was awarded a Nobel Prize for Physiology or Medicine in 1997 for discoveries, including the ‘prion’ theory, that could lead to new treatments of dementia-related diseases, including Alzheimer's and Parkinson's diseases. In 1982, he discovered prions – an entirely new type of disease-causing agent much smaller than viruses and consisting of only a simple protein. Prions have been linked to a number of fatal degenerative brain diseases in mammals, including kuru and Creutzfeldt–Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep and goats.
Prusiner began studying CJD and then scrapie in the early 1970s when he was a neurologist at the University of California School of Medicine, San Francisco. The work of the US virologist D Carleton Gadjusek and others had shown that these diseases could be transmitted using extracts of diseased brains, and at first Prusiner believed that the agent concerned would be a small virus. However, evidence from brain extracts indicated that the agent – unlike viruses and all other known infectious agents – did not contain nucleic acids (the genetic materials RNA or DNA). In 1982 he reported that he and his colleagues had succeeded in producing a preparation (from diseased hamster brains) that contained a single infectious agent. He concluded that the agent, which he called a prion (an acronym derived from ‘proteinaceous infectious particle’), consisted only of protein and lacked genetic material. His paper was greeted with scepticism and initiated a search for the missing nucleic acid, but in 1983 Prusiner and his colleagues isolated the prion protein, which they found to be a single protein (PrP), and in the following year, a section of its amino acid sequence was determined. By the early 1990s, Prusiner's prion theory had gained widespread acceptance.
In 1984 Prusiner found that the gene encoding the prion protein occurred normally in all the mammals he had tested, including humans. Subsequently, it was found that the protein can fold into two different forms: a normal, harmless form and an abnormal but more stable, disease-causing form. The latter is infectious and causes a chain reaction that induces the normal protein to fold into the disease-causing form. These aggregate to form long filaments that gradually damage the tissue of the central nervous system. In 1989 Prusiner found that the hereditary forms of CJD and Gerstmann–Sträussler–Scheinker disease (a rare form of hereditary dementia) are due to mutations in the prion gene.
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