2010 Fiscal Year Final Research Report
The study of diagnosis for Parkinson disease at early-stage using with monoclonal antibodies against oxidized DJ-1.
| Project/Area Number |
21890315
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Public health/Health science
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| Research Institution | Mukogawa Women's University (2010)
National Institute of Advanced Industrial Science and Technology (2009) |
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Principal Investigator |
AKAZAWA Yoko Mukogawa Women's University, 薬学部, 助手 (50549897)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 蛋白質 / 脳神経疾患 / プロテオーム / 老化 |
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| Research Abstract |
The molecular mechanisms leading to neurodegeneration in Parkinson disease (PD) remain elusive, although many studies of evidence have indicated that oxidative stress and impairment of protein degradation system, resulting in cell death. However, idiopathic PD is essentially diagnosed clinically. The development of biomarkers for PD would afford many advantages : early diagnosis and identification of subgroups of PD. DJ-1 had recently found to be causative gene for a familial form of PD. Cysteine residue at position 106 (Cys-106) in DJ-1 was found to be oxidized preferentially under oxidative stress. In the present study, we developed specific antibodies against Cys-106-oxidized DJ-1 and a competitive enzyme-linked immunosorbent assay (ELISA) for detecting oxidized DJ-1, and measured blood levels of oxidized DJ-1 in PD patients. It was observed that the level and an aggregated form of oxidized DJ-1 in erythrocytes of unmedicated PD patients were markedly higher than mediacted PD patients and healthy subjects. Furthermore, we observed that the treatment of mice with PD model compounds results in a significant elevation of oxidized DJ-1 in erythrocytes and its positive cells in the substantia nigra in a dose-and time-dependent manner. These results suggest the involvement of oxidative modification of DJ-1 in the pathogenesis of PD.
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