Parkinson's disease is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1 has been identified as a causative gene of a familial form of Parkinson's disease, PARK7, and plays a significant role in antioxidative defense, protecting cells from oxidative stress.
A cysteine residue of DJ-1 at position 106 (Cys-106) is preferentially oxidized under oxidative stress. This reactive Cys-106 plays a critical role in the biological function of DJ-1, which could act as a sensor of oxidative stress by regulating antioxidative defense depending on Cys-106 oxidation.
Thus, the levels of Cys-106-oxidized DJ-1 (oxDJ-1) could be a possible biomarker of oxidative stress. This chapter focuses on the properties of DJ-1 and oxDJ-1 levels as a biomarker of Parkinson's disease.
The usability of these biomarkers to prevent and treat this neurodegenerative disease is discussed. Further, this section deals with the importance of identifying a biomarker of early-phase Parkinson's disease.
Finally, this chapter summarizes the features of oxDJ-1 levels in the brain and blood as a biomarker candidate for early-phase Parkinson's disease based on our results using oxDJ-1-specific antibodies.
The significance of Oxidized DJ-1 as a Biomarker
Accumulating evidence indicates that DJ-1 oxidation in erythrocytes and the brain is a common phenomenon in patients with PD and animal models of PD, particularly at early phases.
Although it is not clear whether oxDJ-1 in erythrocytes of PD patients is derived from the brain or erythrocytes, the measurement of oxDJ-1 in erythrocytes as a biomarker of PD has several benefits, such as convenience and versatility.
At present, the movement dysfunction associated with PD is “just the tip of the iceberg,” and several other changes are known, including the formation of LBs in the peripheral tissues of patients with PD. Peripheral nervous system disorders, such as reduced cardiac uptake of radiolabelled MIBG, have also been used for the diagnosis of PD.
An association between oxDJ-1 levels in erythrocytes and cardiac uptake of MIBG has been recognized. Thus, changes in peripheral tissues could be utilized as biomarkers for the diagnosis of early-phase PD.
The substantial relationship between the central nervous system and peripheral tissues in the pathology of PD remains unclear. To elucidate this relationship is not only critical for the understanding of PD pathology but also for the development of a reliable biomarker of PD.
Several studies indicate a relationship between DJ-1 oxidation, oxidative stress, and the onset and progression of PD. The importance of the prevention of oxidative stress in PD is recognized.