Abstract
Parkinson’s disease (PD) is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1, the product of the causative gene of a familial form of PD, plays a significant role in anti-oxidative defence to protect cells from oxidative stress. DJ-1 undergoes preferential oxidation at the cysteine residue at position 106 (Cys-106) under oxidative stress. Here, using specific antibodies against Cys-106-oxidized DJ-1 (oxDJ-1), it was found that the levels of oxDJ-1 in the erythrocytes of unmedicated PD patients (n = 88) were higher than in those of medicated PD patients (n = 62) and healthy control subjects (n = 33). Elevated oxDJ-1 levels were also observed in a non-human primate PD model. Biochemical analysis of oxDJ-1 in erythrocyte lysates showed that oxDJ-1 formed dimer and polymer forms, and that the latter interacts with 20S proteasome. These results clearly indicate a biochemical alteration in the blood of PD patients, which could be utilized as an early diagnosis marker for PD.
Highlights
DJ-1 is implicated as the causative gene of a familial form of Parkinson’s disease (PD), namely PARK7, and it plays an important role in anti-oxidative defence, protecting cells from oxidative stress[1,2]
These results suggest that the levels of oxidized DJ-1 in erythrocyte increase during early-phase PD, in unmedicated PD patients
DJ-1, the product of the causative gene of a familial form of PD, undergoes preferential oxidation of cysteine at position 106 (Cys-106) under oxidative stress, and this reactive Cys is necessary for the anti-oxidative function of DJ-1
Summary
DJ-1 is implicated as the causative gene of a familial form of Parkinson’s disease (PD), namely PARK7, and it plays an important role in anti-oxidative defence, protecting cells from oxidative stress[1,2]. The acidic spot shift of DJ-1 observed by 2D-PAGE analysis of cells under oxidative stress arises from oxidation of the cysteine residue to either Cys-SO2H or Cys-SO3H. In this regard, there have been a number of attempts to develop in vivo imaging markers for dopamine neurons and iron levels in the substantia nigra[28,29]. Immunohistochemical analysis suggests that, in the substantia nigra of midbrain, oxDJ-1 levels increase in the early phases of PD and decrease at later stages of PD patients with dementia who have already lost almost all of their dopamine neurons[31]. The evidence suggests that DJ-1 oxidation in erythrocytes occurs in both PD patients and in animal models of PD
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