Project Overview

Parkinson’s disease is a neurodegenerative movement disorder. At the cellular level, one of the main features of Parkinson’s disease is the clumping of a protein called alpha-synuclein. The disease gets worse as this clumping phenomenon spreads from one neuron to the next. A second feature of Parkinson’s disease is defects in lipid metabolism. This includes accumulation of a lipid called glucosylceramide. How lipids affect the spread of alpha-synuclein is poorly understood.

We discovered that accumulation glucosylceramide leads to the formation of tiny vesicles that are released by neurons. We hypothesize that these vesicles contain alpha-synuclein and transfer the toxic protein to neighboring neurons. This study will test if 1) there are more vesicles formed in Parkinson’s disease neurons, 2) if vesicle formation can be prevented by targeting lipid metabolism pathways, and 3) if vesicles contain toxic alpha-synuclein. A strength of our study comes from our use of real-time imaging of vesicles as they form using advanced microscopy. We will use multiple model systems including Parkinson’s disease patient cells grown into neurons and mice. Ultimately, we hope to block vesicle formation to prevent the progression of Parkinson’s disease pathology into new brain regions. However, a fundamental characterization is first required.

Principal Investigator

Maria Ioannou , University of Alberta

Partners and Donors

Azrieli Foundation