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β 42是一种可高度聚集的致病性分子，可引发阿尔茨海默病。β 42淀粉样蛋白是由分泌酶产生的。在这项研究中，我们进行了体外研究，纯化的γ分泌酶和底物包括淀粉样β 42混合。我们进行了酶动力学研究，阐明了淀粉样蛋白是如何产生的。我们还分析了淀粉样蛋白β 42抑制化合物（γ分泌酶调节剂）的功能。我们还研究了γ分泌酶产生NICD的过程。

项目成果

Transcriptome analysis of distinct mouse strains reveals kinesin light chain-1 splicing as an amyloid-β accumulation modifier

• DOI: 10.1073/pnas.1307345111
• 发表时间: 2014-02-18
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Morihara, Takashi;Hayashi, Noriyuki;Takeda, Masatoshi
• 通讯作者: Takeda, Masatoshi

Absolute Quantitation of Low Abundance Plasma APL1β peptides at Sub-fmol/mL Level by SRM/MRM without Immunoaffinity Enrichment

• DOI: 10.1021/pr4010103
• 发表时间: 2014-02-01
• 期刊: JOURNAL OF PROTEOME RESEARCH
• 影响因子: 4.4
• 作者: Sano, Shozo;Tagami, Shinji;Tomonagat, Takeshi
• 通讯作者: Tomonagat, Takeshi

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

APL2βの産生メカニズムの解析(1)APLP2はプレセニリン1と2で異なる切断を受ける

APL2β的产生机制分析（1）APLP2被早老素1和2不同的裂解

• 发表时间: 2012
• 作者: Morihara;T.;Hayashi;N.;Yokokoji;M.;Akatsu;H.;Silverman;MA.;Kimura;N.;Saito;Y.;Suzuki;T.;Yanagida;K.;Tanaka;T.;Kazui;H.;Kudo;T.;Kodama;TS.;Sato;M.;Hashimoto;R.;Tagami;S.;Okochi;M.;Ytoh;N.;Nishitomi;K.;Takamura;H.;Kat;柳田寛太
• 通讯作者: 柳田寛太

Identification and quantitative analysis of APL1ß peptides in human cerebrospinal fluid (CSF)

人脑脊液 (CSF) 中 APL1ß 肽的鉴定和定量分析

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