Abstract
DJ-1, the product of a causative gene of a familial form of Parkinson’s disease (PD), undergoes preferential oxidation of cysteine residue at position 106 (Cys-106) to sulfinic acid (Cys-SO2H) under oxidative stress. Using specific antibodies against Cys-106-oxidized DJ-1, we developed immunological methods to detect oxDJ-1, such as western blotting, enzyme-linked immunosorbent assay (ELISA), and immunostaining. In the brain of PD patients, the oxDJ-1 immunoreactivity (IR) was evident in the substantia nigra of the midbrain, and DJ-1 oxidation in dopaminergic nigral neuronal cells significantly increased before onset of PD. In the blood of PD patients, the levels of oxDJ-1 in the erythrocytes were also high during early-phase PD. These results suggest the increase in DJ-1 oxidation in erythrocytes and the brain of patients with PD, particularly at early phases. In this presentation, we will discuss the biochemical changes in peripheral tissues of early-phase PD, which could be used as a marker for the early diagnosis of PD. In addition, we will show that oxDJ-1 interacts with the 20S proteasome, and discuss the relation of DJ-1 to the accumulation of modified proteins in PD patients.
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