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The study of diagnosis for Parkinson disease at early-stage using with monoclonal antibodies against oxidized DJ-1.

使用抗氧化DJ-1单克隆抗体早期诊断帕金森病的研究。

基本信息

批准号：
21890315
负责人：
AKAZAWA Yoko
金额：
$ 1.57万
依托单位：
Mukogawa Women's University (2010)National Institute of Advanced Industrial Science and Technology (2009)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Research Activity Start-up
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2010
项目状态：
已结题

项目摘要

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.

帕金森病（Parkinson disease，PD）神经退行性变的分子机制尚不清楚，但大量研究表明，氧化应激和蛋白质降解系统受损，导致细胞死亡。然而，特发性PD基本上是临床诊断的。PD生物标志物的开发将提供许多优势：早期诊断和PD亚组的识别。DJ-1是近年来发现的一种家族性PD的致病基因。DJ-1中106位半胱氨酸残基（Cys-106）在氧化应激下被优先氧化。在本研究中，我们开发了针对Cys-106-氧化DJ-1的特异性抗体和用于检测氧化DJ-1的竞争性酶联免疫吸附试验（ELISA），并测量PD患者血液中氧化DJ-1的水平。观察到未用药的PD患者的红细胞中氧化DJ-1的水平和聚集形式显著高于用药的PD患者和健康受试者。此外，我们观察到用PD模型化合物治疗小鼠导致黑质中红细胞及其阳性细胞中氧化DJ-1以剂量和时间依赖性方式显著升高。这些结果表明DJ-1的氧化修饰参与PD的发病机制。