Grant: Operating Grant

Parkinson's disease (PD) is a neurological disorder which is caused by the progressive loss of brain cells (neurons) in areas of the brain involved with movement. The loss of these neurons results in a deficiency of a chemical called dopamine, which is essential for movement. Consequently, PD is characterized by tremor in the extremities, difficulty in initiating voluntary movements, and rigidity. The cause of this debilitating disorder remains a mystery, and although drugs such as the dopamine precursor, L-DOPA, provide symptomatic relief, there are no treatments which can prevent the onset and progression of PD. An important focus of current studies is on the potential benefits of agents which can protect brain cells from the destructive effects of toxic substances called free radicals, which are caused by environmental neurotoxins, such as pesticides, and thought to be involved in the onset of PD. One such neuroprotective agent is the hormone melatonin, which exerts antioxidant effects and modulates the production of neurotrophic factors, which play a crucial role in the survival of dopamine-producing cells in the brain. We have reported that chronic treatment with low (normal or physiological) doses of melatonin protects and maintains brain dopamine-producing cells in an animal model of PD. In this project, we will use animals lacking melatonin targets or receptors to determine the sites and mechanisms involved in the preservation of dopamine neurons by this hormone. The Parkinson Society Canada has estimated that there are about 100,000 Canadians with PD. The associated mortality is more than double that of healthy Canadians. There is also a major cost to society and the health care system, which is predicted to increase with the aging of the Canadian population. Therefore, it is essential to discover novel and effective treatments, as proposed in this application, for preventing or reversing the onset and progression of PD.