Grant: Project Grant

Parkinson's Disease (PD) is the second most prevalent neurodegenerative disease worldwide and the most common human movement disorder, affecting over 100,000 Canadians. Characterized by a progressive decline in voluntary movement, motor function eventually dissipates, and patients lose the ability to move. To date, there is no effective treatment capable of halting or reversing disease pathology. While many brain regions are affected in PD, dopamine producing neurons in the midbrain are most susceptible to degeneration. As the disease progresses, evidence suggests that pathology spreads from this area through anatomically linked regions of the brain. Our work has shown that PD patient derived brain cells can transmit pathology in a cell to cell manner, triggering disease in previously healthy cells. The current project will focus on determining how pathogenic material can move from diseased cells into a healthy brain. The protein, alpha-synuclein, accumulates in the brain of PD patients and is the primary component of Lewy Bodies, which are the primary hallmark of the disease. For disease to spread, alpha-synuclein must move between cells and trigger formation of Lewy Bodies in new areas of the brain. We believe this results from dysfunction in a cell survival process called autophagy, that functions to clean the cell of dysfunctional components and debris. We find that alpha-synuclein interacts with and perturbs components of the autophagy pathway. As result of the cell being unable to clean debris, the cell releases it into the surrounding area where is can affect neighboring cells. We will therefore determine if alpha-synuclein inhibits autophagy in PD and if stopping the release of alpha-synuclein slows the spread of disease. If successful, this study will yield a target drug development against PD.