Analysis of presenilin gamma-secretase function on Abeta and NICD generation

早老素γ分泌酶对Abeta和NICD生成的功能分析

• 批准号: 23591703
• 负责人: TAGAMI Shinji
• 金额: $ 3.24万
• 依托单位: Osaka University
• 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-23591703/
• 关键词: アルツハイマー病; アミロイドβ; γセクレターゼ; Notchシグナル; プレセニリン; Alzheimer disease; gamma secretase; amyloid beta; presenilin; Notch-1; GSM; APLP1; βAPP

Amyloid beta42 is a highly aggregatable and pathogenic molecule which triggers Alzheimer disease. Amyloid beta42 is generated by gamma-secretase. In this study, we performed in vitro study in which purified gamma secretase and substrates including amyloid beta42 are mixed. We performed enzyme kinetics study and elucidated how amyloid beta is generated. We also analyzed how amyloid beta42 inhibiting compounds (gamma secretase modulators) function. We also investigated NICD generating process by gamma secretase.

淀粉样蛋白β42是一种高度聚集的致病分子，可触发阿尔茨海默氏病。淀粉样蛋白β42由伽马分泌酶产生。在这项研究中，我们进行了体外研究，其中混合了纯化的γ泌尿液和包括淀粉样蛋白β42在内的底物。我们进行了酶动力学研究，并阐明了如何产生淀粉样蛋白β。我们还分析了淀粉样蛋白β42如何抑制化合物（γ泌尿酶调节剂）功能。我们还研究了伽马分泌酶的NICD生成过程。

项目成果

γ-Secretase Modulators and Presenilin 1 Mutants Act Differently on Presenilin/γ-Secretase Function to Cleave Aβ42 and Aβ43

• DOI: 10.1016/j.celrep.2012.11.028
• 发表时间: 2013-01-01
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Okochi, Masayasu;Tagami, Shinji;Takeda, Masatoshi
• 通讯作者: Takeda, Masatoshi

γセクレターゼ修飾薬のアルツハイマー病予防薬としての理論と実際

γ-分泌酶调节剂作为阿尔茨海默病预防药物的理论与实践

• 发表时间: 2012
• 作者: 大河内正康;田上真次;柳田寛太;児玉高志;武田雅俊
• 通讯作者: 武田雅俊

CSF APL1β28 is a possible surrogate marker for Aβ42 production in human brains

CSF APL1β28 可能是人脑中 Aβ42 产生的替代标记

• 发表时间: 2013
• 作者: Naoki Mizuta;Masayasu Okochi;Shinji Tagami,Kanta Yanagida;Takashi Kodama,Toshihisa Tanaka;Takashi Morihara;Takashi Kudo;Masatoshi Takeda
• 通讯作者: Masatoshi Takeda

Degradation of extracellular Aβ42/43 in human brain and cultured cells

人脑和培养细胞中细胞外 Aβ42/43 的降解

• 发表时间: 2013
• 作者: Naoki Mizuta;Masayasu Okochi;Shinji Tagami;Kanta Yanagida;Takashi Kodama;Mako Takami;Yasuo Ihara;Daisuke Kanayama;Takashi Morihara;Takashi Kudo;Toshihisa Tanaka;Masatoshi Takeda
• 通讯作者: Masatoshi Takeda

Chracterization of brain APL2β, an Aβ-like peptide produced from APLP2

大脑 APL2β（一种由 APLP2 产生的 Aβ 样肽）的表征

• 发表时间: 2012
• 作者: Masayasu Okochi;Kanta Yanagida;Shinji Tagami;Takashi Kodama;Shozo Sano,Takeshi Tomonaga;Takaomi C.Saido;Masatoshi Takeda
• 通讯作者: Masatoshi Takeda