Parkinson's disease (PD) is a chronic, progressive neurological disorder that affects more than one million people in the U.S. Oxidative stress is thought to play a key role in the pathogenesis of PD. Dopamine itself is susceptible to auto-oxidation and forms reactive oxygen species (ROS) and quinones that can form free and protein-bound cysteinyl adducts, the latter of which can lead to alterations in protein function. Numerous epidemiological studies have shown that organochlorine pesticide exposure is a significant risk factor for PD. However, the mechanism(s) by which OCs increase the risk of PD is unknown. Alterations in dopamine homeostasis and storage may increase cytosolic levels of dopamine leading to oxidative damage. Using in vitro primary and organotypic cultures as well as in vivo oral dosing studies, we propose to test the hypothesis that altered DA homeostasis and oxidative stress play a role in the link between OC exposure and PD. In addition, we will test the hypothesis that PD is associated with elevated brain pesticide levels by measuring pesticide levels in nervous tissue from patients with PD and their aged-matched controls.
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