Stanley B. Prusiner
University of California, San Francisco
Election Year: 1992
Primary Section: 41, Medical Genetics, Hematology, and Oncology
Secondary Section: 24, Cellular and Molecular Neuroscience
Membership Type: Member
Prion diseases are fatal neurodegenerative disorders afflicting humans and other mammals. Uniquely, these diseases are manifest as sporadic, inherited, and infectious illnesses. Recently, investigation of prion disorders has taken on new significance as atypical causes of a human prion disease, known as Creutzfeldt-Jakob disease (CJD), have been reported in England, possibly contracted through consumption of beef from cows afflicted with bovine spongiform encephalopathy, or "mad cow disease" as it is often called. For many years, investigators thought that prion diseases were caused by a slow acting virus, but due largely to work carried out at UCSF beginning in 1974, the concept that these diseases are caused by prions has emerged. The term prion was introduced in 1982 to distinguish this class of infectious pathogens from viruses and viroids. In the intervening years, studies have shown prions are composed largely, if not entirely, of an abnormal isoform of the prion protein which is encoded by a chromosomal gene. Prion diseases appear to be caused by a conformational transition of the normal, cellular prion protein (PrPc) into a pathogenic isoform (PrPsc). UCSF is a major center for the study of prion diseases. Studies on prion epidemiology, genetics, molecular biology, cell biology, and protein structure are in progress. In recent years, much work has focused on the creation of transgenic mice expressing mutant and foreign forms of PrP. These constitute a particularly powerful tool for modeling the disease. Specific topics under investigation include: (1) molecular structure and conformational transitions of PrPc and PrPsc; (2) mechanism of prion propagation; (3) molecular basis of prion "strains" and diversity; (4) pathogeneis of prion diseases of humans and other mammals; and (5) development of effective drugs for preventing and treating prion diseases.