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.

通过对阿尔茨海默病患者脑内不溶于十二烷基硫酸钠的物质进行生化检测，我们通过克隆的方法鉴定了人α-突触核蛋白。α-突触核蛋白基因的错义突变是家族性帕金森病和路易体痴呆的致病基因。然而，α-突触核蛋白的生理功能仍然难以捉摸。在目前的研究中，我们已经证明α-突触核蛋白定位于神经元线粒体的内膜，并且α-突触核蛋白与腺苷转运体结合。提示α-突触核蛋白可能通过线粒体通透性转换孔调节ATP的产生。利用体外细胞培养系统，我们发现α-突触核蛋白促进细胞增殖并影响早期神经突起的生长。结果表明，这些作用是通过α-突触核蛋白组装微管形成微管实现的。

项目成果

C-terminal part of α-synuclein mediates its activity in promoting proliferation of dopaminergic cells

• DOI: 10.1007/s00702-011-0592-y
• 发表时间: 2011-02
• 期刊: Journal of Neural Transmission
• 影响因子: 3.3
• 作者: JuanJuan Yin;Junyan Han;Chen Zhang;Qiu-lan Ma;Xin Li;F. Cheng;Guangwei Liu;Yao-hua Li;K. Uéda;P. Chan;Shun Yu

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

Increase expression of α-synuclein in aged human brain associated with neuromelanin accumulation

• DOI: 10.1007/s00702-011-0636-3
• 发表时间: 2011-04
• 期刊: Journal of Neural Transmission
• 影响因子: 3.3
• 作者: Q. Xuan;Sheng-li Xu;D. Lu;Shun Yu;Ming Zhou;K. Uéda;Ye-qing Cui;Bo Zhang;P. Chan

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