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. 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. 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. The pentose phosphate pathway (PPP) is a metabolic pathway that functions that is critical for neuronal health. One of the key roles of the PPP is the generation of NADPH. NADPH is a reducing agent that plays a critical role in protecting cells from oxidative stress by helping to regenerate glutathione (an important antioxidant) and participating in various biosynthetic processes. We find alpha-synuclein is a critical component of the PPP and that it functions to maintain dopamine homeostasis. The proposal will explore whether a break in this link causes the early loss of dopamine that leads to PD.