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Identification and functional analysis of gamma-secretase-modulating factors

Research Project

Project/Area Number 24659034
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionNagasaki University

Principal Investigator

IWATA Nobuhisa  長崎大学, 医歯薬学総合研究科(薬学系), 教授 (70246213)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアルツハイマー病 / アミロイドβペプチド / γセクレターゼ / プレセニリン / 活性調節 / γ-セクレターゼ / 亜鉛トランスポーター / 亜鉛 / プロテオリシス
Outline of Final Research Achievements

We previously found that a production ratio of Aβ42/Aβ40 was decreases in a differentiation day-dependent manner when we differentiated human iPS cells to neuronal cells, suggesting that a γ-secretase-modulating factor may be expressed in the cells, because gene expression of any component of the γ-secretase complex was not changed. So, we analyzed a neuronal differentiation day-dependent gene expression profile and selected some genes as a tentative candidate gene of γ-secretase-modulating factor. We cloned the tentative candidate genes, transfected them into neuronal cells, and measured a production ratio of Aβ42/Aβ40 in cultured medium. To date, we identified one of zinc transporter as γ-secretase-modulating factor. Now, we are planning to confirm this function of the zinc transporter using some different experimental paradigms.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (7 results)

All 2015 2014 2013 Other

All Presentation (5 results) (of which Invited: 3 results) Remarks (2 results)

  • [Presentation] iPS細胞を用いたアルツハイマー病の病態解析2015

    • Author(s)
      岩田修永
    • Organizer
      JST-再生医療実現拠点ネットワークプログラム [疾患特異的iPS細胞を活用した難病研究]・JST-CREST[iPS細胞領域]合同シンポジウム
    • Place of Presentation
      東京(東京国際フォーラム)
    • Year and Date
      2015-02-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病の病態メカニズムと新たな治療の試み2014

    • Author(s)
      岩田修永
    • Organizer
      沖縄認知症ネットワーク研究会第24回学術集会
    • Place of Presentation
      那覇市(沖縄県医師会館)
    • Year and Date
      2014-11-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いたアルツハイマー病の発症機構と遺伝子治療2014

    • Author(s)
      岩田修永
    • Organizer
      長崎県小児科医会総会 学術講演会
    • Place of Presentation
      長崎市(ホテルニュー長崎)
    • Year and Date
      2014-04-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] iPS細胞の神経分化過程におけるAβ42/Aβ40産生比の変化とその責任遺伝子の解析2014

    • Author(s)
      浅井 将、中野 梨絵、小出 恵理子、森田 知樹、荒木 希、渡邊 かおり、八幡 直樹、関 恒慶、小林 千浩、戸田 達史、城谷 圭朗、井上 治久、岩田 修永
    • Organizer
      iPS細胞研究の今 「iPS細胞」研究支援3制度合同シンポジウム2014
    • Place of Presentation
      東京(日本科学未来館)
    • Related Report
      2013 Research-status Report
  • [Presentation] 神経分化過程におけるAβ40とAβ42の産生比の変化とその責任遺伝子の解析2013

    • Author(s)
      浅井 将、中野 梨絵、荒木 希、渡邊 かおり、八幡 直樹、関 恒慶、小林 千浩、戸田 達史、城谷 圭朗、井上 治久、岩田 修永
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Related Report
      2013 Research-status Report
  • [Remarks] 研究概要/研究テーマ/ネプリライシンおよびセクレターゼの活性調節分子の探索

    • URL

      http://www.ph.nagasaki-u.ac.jp/lab/biotech/research.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 研究概要/研究テーマ/ネプリライシンおよびセクレターゼの活性調節分子の探索

    • URL

      http://www.ph.nagasaki-u.ac.jp/lab/biotech/research.html

    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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