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.

对患有阿尔茨海默病的大脑进行 SDS 不溶性物质的生化检查后，我们通过 cDNA 克隆鉴定了人类 α-突触核蛋白。 α-突触核蛋白基因的一些错义突变被发现是家族性帕金森病和家族性路易体痴呆患者的致病基因。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，我们发现α-突触核蛋白定位于神经元线粒体的内膜，并且α-突触核蛋白结合腺苷酸易位蛋白。这表明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。使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生长。结果表明，这些效应是通过 α-突触核蛋白组装微管蛋白形成微管而产生的。

项目成果

Alpha-Synuclein promotes early neurite outgrowth in primary cultured neurons

α-突触核蛋白促进原代培养神经元的早期神经突生长

• DOI: 10.1007/s00702-013-0999-8
• 发表时间: 2013
• 作者: Liu G; Wang P; Li X; Li Y; Xu S; Ueda K; Chan P; Yu S
• 通讯作者: Yu S

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

• 发表时间: 2013
• 作者: Liu G; Wang P; Li X; Li Y; Xu S; Ueda K; Chan P; Yu S
• 通讯作者: Yu S

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

α-突触核蛋白促进网格蛋白介导的 NMDA 受体内吞作用并减弱 NMDA 诱导的多巴胺能细胞死亡

• DOI: 10.1111/j.1471-4159.2011.07460.x
• 发表时间: 2011
• 作者: Cheng F; Li X; Li Y; Wang C; Wang T; Liu G; Baskys A; Uéda K; Chan P; Yu S
• 通讯作者: Yu S

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

α-突触核蛋白的 C 末端部分介导其促进多巴胺能细胞增殖的活性

• DOI: 10.1007/s00702-011-0592-y
• 发表时间: 2011
• 作者: Yin J; Han J; Zhang C; Ma QL; Li X; Cheng F; Liu G; Li Y; Uéda K; Chan P; Yu S
• 通讯作者: Yu S

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

α-突触核蛋白的 C 末端部分介导其促进多巴胺能细胞增殖的活性。

• 发表时间: 2011
• 作者: Yin J; Han J; Zhang C; Ma QL; Li X; Cheng F; Liu G; Li Y; Ueda K; Chan P; Yu S
• 通讯作者: Yu S