Oxidized DJ-1 as a possible biomarker of Parkinson’s disease

摘要

Parkinson’s disease is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1 is a causative gene of a familial form of Parkinson’s disease, namely PARK7, and plays a significant role in antioxidative defense to protect the cells from oxidative stress. DJ-1 undergoes preferential oxidation at the cysteine residue at position 106, Cys-106, under oxidative stress. The critical role of Cys-106 in the biological function of DJ-1 has been demonstrated, and recent studies indicate that DJ-1 acts as a sensor of oxidative stress by regulating the gene expression of antioxidative defense. Specific antibodies against Cys-106-oxidized DJ-1 have been developed, and the generation of oxidized DJ-1 in cellular and animal models of Parkinson’s disease has been investigated. This review focuses on the role of DJ-1 in antioxidative defense and the importance of oxidizable Cys-106 in its function. The significance of the identification of early-phase Parkinson’s disease biomarkers and the nature of oxidized DJ-1 as a biomarker for Parkinson’s disease are discussed here.