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Functional analysis of DJ-1, a causative gene product for familial Parkinson's disease

家族性帕金森病致病基因产物 DJ-1 的功能分析

基本信息

批准号：
17590049
负责人：
TAIRA Takahiro
金额：
$ 2.24万
依托单位：
University of Yamanashi
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

DJ-1 has recently been shown to be responsible for onset of familial Parkinson's disease (PD), PARK7. DJ-1 has been shown to play roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to trigger onset of PD. In this study, a recombinant DJ-1 protein was administrated into the brain of PD model rats that had been injected to 6-hydroxydopamine (6-OHDA) in the left substantia nigra. PD phenotypes, including dopaminergic neuron death both in the substantia nigra and striatum, decrease in dopamine and dopamine transporter levels in the striatum, and motor abnormality, were dramatically improved by wild-type DJ-1 but not L166P DJ-1, a mutant form of DJ-1 found in PD patients. Furthermore, production of reactive oxygen species and cell death induced by 6-OHDA in SH-SY5Y cells were inhibited by addition of the recombinant DJ-1. These findings suggest that DJ-1 is a therapeutic target for PD.

DJ-1最近被证明与家族性帕金森病(PD)Park7的发病有关。DJ-1已被证明在转录调节和抗氧化应激中发挥作用，其功能的丧失被认为是触发帕金森病发病的原因。本研究将重组DJ-1蛋白注入帕金森病模型大鼠左侧黑质6-羟基多巴胺(6-OHDA)。野生型DJ-1可显著改善PD的表型，包括黑质和纹状体的多巴胺能神经元死亡、纹状体多巴胺和多巴胺转运体水平降低以及运动异常，但不能显著改善PD患者中发现的DJ-1的突变形式L166P DJ-1。此外，重组DJ-1还能抑制6-OHDA诱导的SH-SY5Y细胞产生活性氧和细胞死亡。这些发现表明DJ-1是帕金森病的治疗靶点。

项目成果

期刊论文数量（39）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone

DOI：
10.1111/j.1471-4159.2006.04440.x
发表时间：
2007-06-01
期刊：
JOURNAL OF NEUROCHEMISTRY
影响因子：
4.7
作者：
Inden, Masatoshi;Kitamura, Yoshihisa;Shimohama, Shun
通讯作者：
Shimohama, Shun

Induction of reactive oxygen species by bisphenol A and abrogation of bisphenol A-induced cell injury by DJ-1

DOI：
10.1093/toxsci/kfi278
发表时间：
2005-11-01
期刊：
TOXICOLOGICAL SCIENCES
影响因子：
3.8
作者：
Ooe, H;Taira, T;Ariga, H
通讯作者：
Ariga, H

Expression profiles of genes in DJ-1-knockdown and L166P DJ-1 mutant cells

DOI：
10.1016/j.neulet.2005.07.053
发表时间：
2005-12-16
期刊：
NEUROSCIENCE LETTERS
影响因子：
2.5
作者：
Nishinaga, H;Takahashi-Niki, K;Ariga, H
通讯作者：
Ariga, H

DJ-1 restores p53 transcription activity inhibited by Topors/p53BP3.

DOI：
10.3892/ijo.26.3.641
发表时间：
2005-03
期刊：
International journal of oncology
影响因子：
5.2
作者：
Y. Shinbo;T. Taira;Takeshi Niki;Sanae M. M. Iguchi-Ariga-Sanae-M.-M.-Iguchi-Ariga-1395935820;H. Ariga
通讯作者：
Y. Shinbo;T. Taira;Takeshi Niki;Sanae M. M. Iguchi-Ariga-Sanae-M.-M.-Iguchi-Ariga-1395935820;H. Ariga