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The analysis of Familial Parkinson's disease gene products and the research for identification of a novel Familial Parkinson's disease gene

家族性帕金森病基因产物分析及家族性帕金森病新基因鉴定研究

基本信息

批准号：
17390256
负责人：
HATTORI Nobutaka
金额：
$ 9.79万
依托单位：
JUNTENDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
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

Parkinson's disease (PD) is the second most common neurodegenerative disorder with a prevalence of 1% in individuals older than 65 years of age. Although the majority of PD cases are sporadic, it is now clear that genetic factors contribute to the pathogenesis of PD. Until now, seven causative genes for familial PD (FPD) have been identified. Considering the clinical phenotypes such as parkinsonism, it would be possible that FPD gene products share a common pathway. As parkin is direct linked to ubiquitin-pathway as an E3, this product is also thought to function for mitochondria. PINK1 and DJ-1 are also associated with mitochondria. Thus, mitochondrion is a target organella for elucidating the pathogenesis of FPD. In the present study, we found a common pathway between α-synuclein, parkin, PINK1, and DJ-1. In contrast, half of the autosomal recessive FPD showed no mutations in the known causative genes Therefore, we continue to perform the linkage study for identification of a novel gene. On the mapping for a causative gene responsible for late onset PD with autosomal recessive mode of inheritance, a few loci for this form of PD could be identified.

帕金森病（PD）是第二大最常见的神经退行性疾病，65岁以上人群的患病率为1%。虽然大多数PD病例是散发的，但现在很清楚遗传因素有助于PD的发病机制。到目前为止，已经确定了家族性帕金森病（FPD）的七个致病基因。考虑到帕金森病等临床表型，FPD基因产物可能具有共同的通路。由于parkin作为E3与泛素通路直接相关，因此该产品也被认为对线粒体起作用。PINK1和DJ-1也与线粒体有关。因此，线粒体是阐明FPD发病机制的靶细胞器。在本研究中，我们发现α-synuclein、parkin、PINK1和DJ-1之间存在共同的通路。相比之下，一半的常染色体隐性FPD在已知的致病基因中没有突变，因此，我们继续进行连锁研究以鉴定新基因。在对具有常染色体隐性遗传模式的迟发性帕金森病致病基因的定位上，可以鉴定出这种形式的帕金森病的几个位点。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease

DOI：
10.1001/jama.296.6.661
发表时间：
2006-08-09
期刊：
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
影响因子：
120.7
作者：
Maraganore, Demetrius M.;de Andrade, Mariza;Van Broeckhoven, Christine
通讯作者：
Van Broeckhoven, Christine

Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher disease patient and a carrier

DOI：
10.1016/j.jns.2006.10.019
发表时间：
2007-01-31
期刊：
JOURNAL OF THE NEUROLOGICAL SCIENCES
影响因子：
4.4
作者：
Kono, Satoshi;Shirakawa, Kentaro;Mizuno, Yoshikuni
通讯作者：
Mizuno, Yoshikuni

Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein Neurotoxicity.

Sept4 是突触前支架和路易体的组成部分，是抑制 α-突触核蛋白神经毒性所必需的。

DOI：
发表时间：
2007
期刊：
Neuron 53
影响因子：
0
作者：
Ihara M;Yamasaki N;Hagiwara A;Tanigaki A;Kitano A;Hikawa R;Tomimoto H;Noda M.;Takanashi M;Mori H;Hattori N;Miyakawa T;Kinoshita M.
通讯作者：
Kinoshita M.

Bispecific antibodies against modified protein and DNA with oxidized lipids.

针对修饰蛋白和氧化脂质 DNA 的双特异性抗体。