Grant: Project Grant

Parkinson's disease is a neurodegenerative disorder. Two main features of Parkinson's disease are the clumping of a protein called alpha-synuclein and inflammation. The disease gets worse as this clumping phenomenon spreads from one neuron to the next. A newly appreciated feature of Parkinson's disease is defects in fat metabolism. How fat affects the spread of alpha-synuclein is poorly understood. We discovered that neurons release small vesicles in Parkinson's disease. We believe that these vesicles spread alpha-synuclein in the disease. This study will test 1) how fats associated with Parkinson's disease affect vesicle formation, 2) if vesicles mediate the spread of toxic alpha-synuclein between cells and 3) if vesicles stimulate inflammation as is seen in the disease. A strength of our study comes from real-time imaging of vesicles as they form. We will use multiple model systems including neurons grown from patient cells and mouse models. We hope this project will reveal new targets for therapies to slow Parkinson's disease progression.