Modulation of the DAT/DJ-1 interaction by oxidative stress

Mental Health and Addictions

Dopamine (DA) is a neurotransmitter that is involved in various neurological systems that affect movement, reward, learning and memory. DJ-1, a gene linked to autosomal recessive early-onset Parkinson’s disease (PD) whose normal physiological function is unknown has been shown to be involved in DA neurotransmission, particularly through the dopamine transporter (DAT). In addition, we have preliminary evidence to suggest a direct interaction between the DAT and DJ-1 and that the functional modification of DAT by DJ-1 may be regulated by oxidative stress. Therefore, to investigate the interaction between DAT and DJ-1 this proposal will pursue to characterize the interaction between DAT and DJ-1 and examine the physiological effect of disrupting the DAT/DJ-1 complex. These studies may reveal how DJ-1 responds to oxidative stress and in turn regulate DAT function. Understanding how the DAT is regulated by DJ-1 may provide insight into the molecular mechanism of PD.