The impact of clinical presenilin mutations on amyloid formation in the brains of familial Alzheimer disease

临床早老素突变对家族性阿尔茨海默病大脑中淀粉样蛋白形成的影响

• 批准号: 22890251
• 负责人: OIKAWA Naoto
• 金额: $ 1.94万
• 依托单位: National Center for Geriatrics and Gerontology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22890251/
• 关键词: 神経変性疾患; 認知症; アルツハイマー病; プレセニリン; γセクレターゼ; アミロイドβプロテイ; アミロイド; ガングリオシド; γセレクターゼ; アミロイドβプロテイン; アミロイドβ蛋白; 膜脂質

To clarify the significance of clinical presenilin mutations in amyloid formation in the brains of familial Alzheimer disease, we examined whetherγ-secretase inhibition, which seems to be induced by the presenilin mutations, alters the levels of membrane lipids, including GM1-ganglioside, which is an inducer of amyloid formation, in vitro. Under pharmacological inhibition ofγ-secretase activity, levels of gangliosides, including GM1-ganglioside, increased at neuritic terminals, which are the initial sites of amyloid formation, of differentiated PC12 cells. This result suggests that clinical presenilin mutations can induce amyloid formation via the alteration of membrane lipid environment in brains.

为了阐明临床早老素突变对家族性阿尔茨海默病大脑中淀粉样蛋白形成的重要性，我们检查了似乎由早老素突变诱导的γ-分泌酶抑制是否改变了膜脂质的水平，包括GM1-神经节苷脂，其是体外淀粉样蛋白形成的诱导剂，在 γ-分泌酶活性的药理抑制下，神经节苷脂（包括 GM1-神经节苷脂）的水平在神经炎末梢增加。这是分化的 PC12 细胞淀粉样蛋白形成的起始位点。这一结果表明，临床早老素突变可以通过改变大脑中的膜脂环境来诱导淀粉样蛋白形成。

项目成果

Inhibition of γ-secretase activity increases ganglioside levels at neuntic terminals of differentiated PC12

抑制 γ 分泌酶活性会增加分化 PC12 神经节末端的神经节苷脂水平

• 发表时间: 2011
• 作者: 及川尚人

Suppression ofγ-secretase activity increases ganglioside levels at neuritic terminals of differentiated PC12

抑制 γ 分泌酶活性会增加分化 PC12 神经末梢的神经节苷脂水平

• 发表时间: 2012
• 作者: Naoto Oikawa;Miho Goto;Kazutaka Ikeda;Ryo Taguchi;Katsuhiko Yanagisawa
• 通讯作者: Katsuhiko Yanagisawa

Inhibition ofγ-secretase activity increases ganglioside levels at neuritic terminals of differentiated PC12

抑制 γ 分泌酶活性会增加分化 PC12 神经末梢的神经节苷脂水平

• 发表时间: 2011
• 作者: Naoto Oikawa;Miho Goto;Kazutaka Ikeda;Ryo Taguchi;Katsuhiko Yanagisawa
• 通讯作者: Katsuhiko Yanagisawa