Shedding a negative image

Abstract

Although the idea of a protein as an infectious agent emerged almost 40 years ago, the hypothesis only became mainstream after Stanley Prusiner's seminal paper describing how proteins could cause disease (Prusiner, 1982). Prusiner, now a professor of neurology at the University of California, San Francisco, USA, won the 1997 Nobel Prize in Physiology or Medicine for his discovery of these proteinaceous infectious particles, known as prions. After some initial resistance, the scientific community has now largely accepted that prions, by misfolding and aggregating into larger clumps, cause neurodegenerative diseases such as scrapie in sheep, bovine spongiform encephalitis (BSE) in cattle and Creutzfeldt–Jakob Disease (CJD) in humans. However, it is only in the past few years that scientists have begun to understand the molecular mechanisms behind infectious proteins. Recent work on how prions propagate their structural conformation by recruiting other proteins helps to explain the pathology behind the neurodegenerative diseases that they cause, and also expands the concept to other proteins and diseases. As scientists gain a better understanding of prions, these proteins are shedding some of their predominantly negative image as pathological aberrations of nature. In fact, prions might have important biological roles in both prokaryotic and higher organisms. An exciting development came earlier this year with the discovery that the ability of prion particles to spread infection depends on their brittleness (Tanaka et al , 2006). Jonathan Weissman, from the Howard Hughes Medical Institute at the University of California, San Francisco, USA, and colleagues showed that the more brittle—and therefore less stable—prion particles break into smaller fragments more frequently. This creates new seeding particles that, in turn, grow into larger aggregates by recruiting new molecules of the same protein. Weissman and his colleagues conducted their studies on yeast prions; although their ability to cause infection is doubted by many …