Parkinson's disease (PD) is the most common neurodegenerative movement disorder, yet current treatments are insufficient to battle worsening symptoms and do little to reverse or halt neuronal cell death. Recently, mutations in the gene encoding DJ-1 have been implicated in an early-onset autosomal recessive form of PD. Multiple lines of evidence have suggested a role for DJ-1 in the cellular defense against oxidative stress, yet the mechanism of action remains unknown. We and others have found that a portion of DJ-1 localizes to the mitochondria and interestingly, mitochondrial deficits have previously been implicated in PD. In addition, mitochondria are known to be the major source of cellular oxidative stress and are also known to play a central role in initiation and execution of apoptosis. This project will seek to characterize the subcellular localization of DJ-1, to identify DJ-1 mitochondrial-binding partners, and to test the hypothesis that DJ-1 is a critical regulator of mitochondria-dependent apoptosis. Understanding the role of DJ-1 within the mitochondria will enhance our understanding of PD pathogenesis and could potentially identify critical molecular pathways, possibly providing new targets for therapeutic intervention. ? ?
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