Grant: China-Canada Joint Health Research Initiative

Parkinson's disease is a brain disorder that impairs ability to move and often progresses to dementia. Degeneration of brain tissue in the midbrain region, specifically neurons which are part of the dopamine neurotransmitter system, is known to be a component of the disease. However, the specific molecular mechanisms causing this degeneration remain largely unknown. Evidence supports the hypothesis that the degeneration seen in Parkinson's is due to susceptibility of dopaminergic neurons to disorganized cell death as a result of increased dopamine oxidation and generation of destructive molecules known as reactive oxygen species. Irregular dopamine concentration plays a role in other brain diseases such as addiction and schizophrenia. Finding ways to modulate dopamine transporter function, the key to regulating dopamine concentration, is a major area of research focus worldwide. Recent preliminary work by Dr. Fang Liu's lab in Canada and Dr. YaoQin Gong's group in China, demonstrates that a protein known as CUL4B enhances dopamine transporter function uptake and dopamine-induced programmed cell death. CUL4B is a member of the cullin family of proteins and can function as a scaffold in organizing a large family of key enzymes. Investigation of how these enzymes regulate the dopamine mechanisms is greatly needed and will: -Reveal molecular mechanisms underlying which CUL4B may modulate dopamine transporter-mediated functions -Provide a molecular framework in which to view CUL4B and dopamine transporter interaction -Provide a potential target for developing new therapies to treat dopamine-associated brain diseases By continuing the Canada-China collaboration, both labs will be able to complete critical work more effectively. Identifying specific targets for therapies to modulate dopamine related diseases is a key step in improving health outcomes for Canadians, Chinese and others around the world who suffer from conditions involving this biological mechanism.