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Involvement in neurodegeneration and cell death of synuclein family protein

突触核蛋白家族蛋白参与神经变性和细胞死亡

基本信息

批准号：
12672119
负责人：
NAKAJO Shigeo
金额：
$ 2.05万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672119/
关键词：
synuclein neunonal cell death neuro-degeneration transgenic mouse アポトーシス神経変性疾患

项目摘要

1) We have produced α-synuclein transgenic (α-syn Tg) mice but there was no significant difference in phenotype between wild and α-syn Tg mice.2) Using α-syn Tg mouse, analysis by DNA array was carried out. The result of DNA array analyzed showed that α-synuclein might affect cell death. Human α-synuclein and mutant cDNAs were introduced in IMR-32 cells. Those cells were treated with various stimuli such as vitamin K3, cisplatin, taxol and retinoic acid. However, α-synuclein did not significantly affect cell death induced by those stimuli in wild and transformed IMR-32 cells.3) To clarify the function of mammal synuclein family proteins, investigation of their in lower animals such as amphibian and reptile was performed. Brain lysates prepared from snake and frog were subjected to 2D-gel electrophoresis and then partial amino acid sequences were determined by LC-MS/MS after in gel digestion with trypsin. Two and one synuclein proteins shown the crossreactivity with pan-antibody produced against bovine β-synuclein were identified in snake and frog, respectively.

1)2）以α-syn Tg小鼠为研究对象，采用基因芯片技术对α-syn Tg小鼠的表型进行分析。DNA芯片分析结果表明，α-synuclein可能影响细胞死亡。将人α-突触核蛋白和突变体cDNA导入IMR-32细胞中。这些细胞用各种刺激物如维生素K3、顺铂、紫杉醇和视黄酸处理。然而，α-synuclein对野生型和转化型IMR-32细胞中由这些刺激物诱导的细胞死亡没有显著影响。3）为了阐明哺乳动物synuclein家族蛋白的功能，对哺乳动物synuclein家族蛋白在两栖类和爬行类等低等动物中的功能进行了研究。将蛇和蛙的脑组织裂解液进行双向电泳，用胰蛋白酶消化后，用LC-MS/MS法测定其部分氨基酸序列。在蛇和蛙中分别鉴定出两种和一种与牛β-突触核蛋白产生的泛抗体具有交叉反应性的突触核蛋白。