Grant: CIHR Clinician Scientist - Phase 2

Parkinson's disease is a disabling neurological disorder that is increasing in prevalence and thus having a growing impact on the Canadian population. This disease results from a process called neurodegeneration in which vulnerable nerve cells in the brain die more rapidly than normal. Neurodegeneration in Parkinson's disease causes the clinical symptoms referred to as parkinsonism which include tremor, rigidity, slowness of movements, and postural instability. There are therapies which can alleviate these symptoms but they are associated with significant side effects. Furthermore, none of our current treatments for Parkinson's disease can slow or stop the death of nerve cells. This is due, in large part, to our limited understanding of the molecules that cause neurodegeneration in Parkinson's disease. The goals of the proposed research program are to elucidate the critical molecules responsible for neurodegeneration in Parkinson's disease and to discover drugs that target these molecules. The research plan is based on three main aims: 1) to identify chemical compounds that target the protein alpha-synuclein, a key player in the neurodegenerative process in Parkinson's disease; 2) to investigate the molecules that regulate neurodegeneration due to alpha-synuclein; and, 3) to characterize molecules previously unexplored for their role in causing parkinsonism, including the proteins paraplegin and spatacsin. The overall outcome of the proposed research will be the elucidation of key molecular mechanisms involved in Parkinson's disease and related disorders. This work will lay the foundation for future studies aimed at developing new treatments for people with Parkinson's disease and thereby lead to improved health outcomes for Canadians affected by this disease.