Function of DJ-1, a causative gene for familial Parkinson's disease PARK7 and oncogene

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DJ-1 has recently been shown to be responsible for onset of familial Parkinson's disease (PD), PARK7. We have shown that DJ-1 plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to trigger onset of PD.(1) A role of DJ-1 in dopamine synthesis.DJ-1 was found to bind to tyrosine hydroxylase and DOPA decarboxylase and enhance their activities. Mutants found in Parkinson's disease (PD) patients lost its activities. Heterozygous mutants worked as dominant negatives towards wild-type DJ 1, suggesting that heterozygous mutants will be risk factors for onset of PD. After oxidation stresses come to cells, a cysteine residue at 106 (C106) of DJ-1 was oxidized to SOH, SO_2H and SO_3H. When C106 was weakly oxidized with SOH, and SO_2H forms, DJ-1 was activated. When C106 was strongly oxidized with the SO_3H forms, DJ-l was inactivated. These findings suggest that DJ-1 is committed to onset of a sporadic form of PD.(2) Pharmaceutical application of DJ-1 and its binding compounds to PD.Injection of DJ-1 protein into the brain of PD model rats dramatically protected neuronal cell death and locomotive defect Furthermore, we have identified several compounds that bind to the C106 region of DJ-1 and these compounds also protected neuronal cell death and locomotive defect in PD model rats. These compounds inhibited strong oxidation of C106 of DJ01, thereby keeping active forms of DJ-1.