Neuro-cell biological studies of alpha-synuclein

α-突触核蛋白的神经细胞生物学研究

• 批准号: 23500408
• 负责人: UEDA Kenji
• 金额: $ 3.33万
• 依托单位: 独立行政法人国立精神・神経医療研究センター (2013)Tokyo Metropolitan Institute of Medical Science (2011-2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23500408/
• 关键词: シヌクレイン; ミトコンドリア; ATP産生; チューブリン; 神経突起伸長; 細胞増殖; ドーパミン; カルパイン; αシヌクレイン; MAP; 微小管; 神経変性

After the biochemical examination of SDS-insoluble materials of the brains with Alzheimer's disease, we identified human alpha-Synuclein by cDNA cloning. Some missense mutations of the gene for alpha-Synuclein were found as causal genes for the patients with familial Parkinson's disease and with familial dementia with Lewy bodies. However, physiological functions of alpha-Synuclein remain elusive. In the present studies, we have shown that alpha-Synuclein is localized in the inner membrane of neuronal mitochondria, and that alpha-Synuclein binds adenylate translocator. It suggests that alpha-Synuclein may regulate the production of ATP through mitochondrial permeability transition pore. Using in vitro cell culture systems, we showed that alpha-Synuclein promotes cell proliferation and affects early neurite outgrowth. It was shown that these effects are through microtubule formation via tubulin assembly by alpha-Synuclein.

在患有阿尔茨海默氏病的大脑的SDS不溶性材料的生化检查后，我们通过cDNA克隆确定了人α-突触核蛋白。发现家族性帕金森氏病患者以及患有路易尸体的家族性痴呆症患者的α-核蛋白基因基因的一些错义突变。但是，α-核蛋白的生理功能仍然难以捉摸。 在目前的研究中，我们表明α-突触核蛋白位于神经元线粒体的内膜中，并且α-突触核蛋白结合腺苷酸易位剂。这表明α-突触核蛋白可以通过线粒体通透性过渡孔调节ATP的产生。使用体外细胞培养系统，我们表明α-突触核蛋白促进细胞增殖并影响早期神经突生长。结果表明，这些作用是通过微管通过微管蛋白组装而通过α-核蛋白形成的。

项目成果

Alpha-synuclein promotes early neurite outgrowth in cultured primary neurons

α-突触核蛋白促进培养的原代神经元的早期神经突生长

• DOI: 10.1007/s00702-013-0999-8
• 发表时间: 2013-02
• 期刊: Journal of Neural Transmission
• 影响因子: 3.3
• 作者: Liu, Guangwei;Wang, Peng;Li, Xin;Li, Yaohua;Xu, Shengli;Ueda, Kenji;Chan, Piu;Yu, Shun
• 通讯作者: Yu, Shun

α-Synuclein promotes clathrin-mediated NMDA receptor endocytosis and attenuates NMDA-induced dopaminergic cell death

• DOI: 10.1111/j.1471-4159.2011.07460.x
• 发表时间: 2011-11-01
• 期刊: JOURNAL OF NEUROCHEMISTRY
• 影响因子: 4.7
• 作者: Cheng, Furong;Li, Xin;Yu, Shun
• 通讯作者: Yu, Shun

Demonstration of three dopamine molecules bound to alopha-synuclein: Implication of oligomerization at the initial stage

三个多巴胺分子与α-突触核蛋白结合的演示：初始阶段寡聚化的含义

• DOI: 10.4236/jbpc.2012.32017
• 发表时间: 2012
• 期刊: J. Biophysical Chem.
• 作者: S Shimotakahara;Y Shiroyama;T Fujimoto;M Akai;T Onoue;H Seki;S Kado;T Machinami;Y Shibusawa;K Ueda;M Tashiro
• 通讯作者: M Tashiro

α-Synuclein functions as a negative regulator for expression of tyrosine hydroxylase

α-突触核蛋白作为酪氨酸羟化酶表达的负调节因子

• 发表时间: 2011
• 期刊: Acta Neurol. Belg.
• 作者: Li YH;Gao N;Ye YW;Li X;Yu S;Yang H;Ueda K;Chan P
• 通讯作者: Chan P