Alpha-synuclein

Parkinson’s Disease (PD) and Alzheimer’s Disease (AD) decrease the quality of life for patients and put strains on families caring for elderly relatives and an already overburdened healthcare system. Except in rare cases where a particular genetic defect has been identified, we do not know what causes PD or AD. However, a hallmark of both diseases is the formation of precipitates of mis-folded proteins. In healthy cells, mechanisms exist for the identification and break-down of mis-folded or otherwise defective proteins. These mechanisms appear to break down or are overloaded in PD and AD. Our research in this area is aimed at trying to figure out the structure and dynamics of the “healthy” stable form of a particular protein associated with PD, α-synuclein. With our collaborators, we have identified a dynamic tetramer of synuclein that appears to resist precipitation and may represent a thermodynamically stable “storage” form of the soluble protein in the cell. We are currently using a combination of NMR and molecular modeling methods that will help us to identify small-molecule drug candidates that stabilize this tetramer in hopes of slowing the onset of PD.