Grant: CIHR Fellowship

Parkinson's disease (PD) is a debilitating neurodegenerative disorder affecting 1 percent of the population over the age of 65 and upwards of 4-5 percent of the population over the age of 85. PD symptoms are physical, cognitive and psychiatric and are caused by the degeneration of a subset of a population of neurons in the brain. There is currently no cure for PD and the most effective treatments have a limited therapeutic window, do not slow the progression of disease, and are not without serious side-effects. To date PD is thought to arise mainly from a spontaneous nature and has not been strongly linked with having a hereditary nature. Work in our group has recently defined genetic determinants of PD. We aim to use this knowledge and examine molecular pathways affected in PD using PD causing genetic mutations as a model. We hypothesize that understanding the cellular pathways that are affected in PD will lead towards therapeutic advancements in the treatment of this disorder. Recently we discovered a mutation associated with the protein VPS35. This protein is part of the retromer, an evolutionarily conserved part of the cellular recycling system that has a high affinity for particular cargoes (other proteins) within the cell. We are currently defining the normal function of this protein in neurons. We find that VPS35 has neuron specific functions that overlap with known cellular pathways affected by other proteins that cause familial PD (LRRK2, RME-8). It is our goal to further define common pathways affected by different PD causing mutations and design assays that will reverse harmful cellular phenotypes we find, using small molecules that may be developed into drugs. This work could have clinical outcomes for all forms of PD assuming that a converging pathway is causing both the familial and sporadic forms of the disease.