Grant: Project Grant

Goal: We recently discovered an anti-oxidant role for parkin as a redox-active molecule in human brain. Its deficiency leads to young-onset Parkinson disease in humans, but not in animals. Wild-type parkin appears essential to human dopamine-producing cells in the midbrain, which make neuromelanin. This selectivity has never been adequately explained. We have found that it is in part due to the synergy between oxidative stress and electrophile radicals (eg, dopamine quinones); parkin directly protects against both stressors. Selectivity is also related to neuromelanin formation, a feature unique to human brain, which parkin participates in. Our stated goal is to further validate parkin's redox functions to delineate therapeutic strategies.