Research Projects
Many degenerative brain diseases, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, and the prion diseases, appear to be caused by abnormal protein folding. The Supattapone laboratory is particularly interested in studying the pathogenesis of prion and Alzheimer's disease. Prions are infectious agents of fatal brain diseases that include: Creutzfeldt Jakob Disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cows, and scrapie in sheep and goats. Interestingly, prions are unorthodox infectious agents because they do not contain nucleic acids. Instead, a membrane-bound glycoprotein called the prion protein (PrP) appears to be the molecule responsible for the transmission of prion disease. A cellular isoform of PrP, designated PrPC, is expressed in all normal mammals. When an animal contracts prion disease, the PrPC molecules in the brain of that animal undergo a conformational change to a pathogenic isoform designated PrPSc. This pathogenic isoform is infectious, promoting conformational change to create more PrPSc molecules, and toxic to neurons. The structure and composition of infectious prions, as well as the mechanisms by which prions replicate and destroy neurons are unknown. These questions represent key areas of investigation for our laboratory. Significant scientific advances made in our laboratory include the de novo formation of infectious prions from defined, non-infectious components in vitro and the indentification of non-proteinaceous prion cofactors.
In a similar manner, Alzheimer's disease is characterized by the formation of brain deposits that contain a misfolded peptide known as beta amyloid. Our laboratory is also investigating the mechanish by which these beta amyloid deposits form and spread in the brain.