Dysregulation of Ubiquitylation in Parkinson's Disease

It is now widely accepted that the ability to maintain appropriate levels of proteins is of fundamental importance to the normal function of neurons and other cells. The levels of many proteins are regulated by attachment of chains of a small protein known as ubiquitin. This marks them for degradation by the proteasome, which is the cell's primary means of breaking down proteins. There is increasing evidence that the ubiquitin proteasome system has altered function in neurodegenerative diseases. This is underscored in Autosomal Recessive Parkinson's Disease by genetic abnormalities in the Parkin gene. Parkin is a member of a class of proteins known as RING finger proteins. The primary function of RING fingers is to help attach ubiquitin to proteins that are destined to be degraded. We will take advantage of our expertise in the ubiquitin system to study the functional interaction of Parkin with other proteins involved in ubiquitin attachment. We will also determine whether there are general abnormalities in the ubiquitin proteasome system in Autosomal Recessive and other forms of Parkinson's Disease. Additionally, we will attempt to explore whether dopamine-producing cells are predisposed to losing normal function of the ubiquitin proteasome system.