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Research for therapeutic application of dominant negative GAPDH molecule on oxidative stress-induced disorder

Research Project

Project/Area Number 22580339
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionOsaka Prefecture University

Principal Investigator

NAKAJIMA Hidemitsu  大阪府立大学, 生命環境科学研究科, 准教授 (30405360)

Co-Investigator(Kenkyū-buntansha) KUWAMURA Mitsuru  大阪府立大学, 生命環境科学研究科, 准教授 (20244668)
Co-Investigator(Renkei-kenkyūsha) HIKIDA Takatoshi  (財)大阪バイオサイエンス研究所, システムズ生物学部門, 研究員 (70421378)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords薬理 / 神経変性疾患 / トランスジェニックマウス / 酸化ストレス / 治療 / 疾病予防・制御 / 新規治療薬開発 / GAPDH / 脳神経疾患 / ドミナントネガティブ分子 / アミロイド
Research Abstract

In the present study, we aim to establish a conditional transgenic mice containing mutant GAPDH (C152A-GPDH), which inhibits oxidative stress-induced cell death mediated by GAPDH aggregation dominant negatively, and to investigate whether therapeutic benefits of C152A-GAPDH might be showedin vivo. As a result, we have succeeded two strains of mice in which the expression of C152A-GAPDH is under the control of a tetracycline-inducible system. And then, we are examining the possibility for therapeutic application of C152A-GAPDH on oxidative stress-induced disorders such as stroke model or methamphetamine-elicited Parkinson disease-like model using the established transgenic mice, compared to that of wild-type mice.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (27 results)

All 2013 2012 2011 2010 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (20 results) (of which Invited: 1 results) Book (1 results) Remarks (4 results)

  • [Journal Article] A rapid, targeted, neuron-selective, in vivo knockdown following a single intracerebroventricular injection of a novel chemically modified siRNA in theadult rat brain.2012

    • Author(s)
      Hidemitsu Nakajima, Takeya Kubo, Yuko Semi, Masanori Itakura, Mitsuru Kuwamura, Takeshi Izawa, Yasu-Taka Azuma and Tadayoshi Takeuchi
    • Journal Title

      J. Biotechnol

      Volume: 157 Pages: 326-333

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A rapid, targeted, neuron-selective, in vivo knockdown following a single intracerebroventricular injection of a novel chemically modified siRNA in the adult rat brain2012

    • Author(s)
      Nakajima H, Kubo T, Semi Y, Itakura M, Kuwamura M, Izawa T, Azuma YT, Takeuchi T
    • Journal Title

      Journal of Biotechnology

      Volume: 152(2) Issue: 2 Pages: 326-333

    • DOI

      10.1016/j.jbiotec.2011.10.003

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Glyceraldehyde-3-phosphate dehydrogenase act as a seed of alfa-synuclein amyloidogensesis in oxidative stress-induced neurotoxicity both in vitro and in vivo2013

    • Author(s)
      Hidemitsu Nakajima, Takeya Kubo, Ayano Fukuhara, Masanori Itakura, Mitsuru Kuwamura, Yasu-Taka Azuma, Takashi Inui, Tadayoshi Takeuchi
    • Organizer
      The 11thInternational Conference On Alzheimer's & Parkinson's Diseases
    • Place of Presentation
      イタリア、フィレンツェ(ポスター発表
    • Year and Date
      2013-03-08
    • Related Report
      2012 Final Research Report
  • [Presentation] Glyceraldehyde-3-phosphate dehydrogenase aggregates accelerates amyloidogensesis of amyloid-β40 and promotes amyloid-・40-induced cell death2013

    • Author(s)
      Takeya Kubo, Hidemitsu Nakajima, Yuko Semi, Satoshi Kume, Masanori Itakura,Shusaku Higashida, Mitsuru Kuwamura, Yasu-Taka Azuma, Takashi Inui and Tadayoshi Takeuchi
    • Organizer
      The 11thInternational Conference On Alzheimer's & Parkinson's Diseases
    • Place of Presentation
      イタリア、フィレンツェ(ポスター発表)
    • Year and Date
      2013-03-07
    • Related Report
      2012 Final Research Report
  • [Presentation] ラットMCAOモデルにおいて、 核移行したGAPDHはPARP-1に直接結合し活性化させる2012

    • Author(s)
      久保岳也、中嶋秀満、Shahani Neelam、東 泰孝、竹内正吉、澤 明
    • Organizer
      第154回日本獣医学会学術集会
    • Place of Presentation
      盛岡(口頭発表)
    • Year and Date
      2012-09-15
    • Related Report
      2012 Final Research Report
  • [Presentation] GAPDHペプチドのアミロイド凝集抑制効果2012

    • Author(s)
      中嶋秀満
    • Organizer
      Bio tech 2012 アカデミックフォーラム
    • Place of Presentation
      東京(口頭発表)
    • Year and Date
      2012-04-25
    • Related Report
      2012 Final Research Report
  • [Presentation] Amyloid-like fibril of GAPDH enhances aggregation and neurotoxicity of a-synuclein2012

    • Author(s)
      久保岳也、瀬見優子、中嶋秀満、田島久男、東 泰孝、竹内正吉「Amyloid-like fibr
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都(口頭発表)
    • Year and Date
      2012-03-14
    • Related Report
      2012 Final Research Report
  • [Presentation] GAPDHペプチドのアミロイド凝集抑制効果2012

    • Author(s)
      中嶋秀満
    • Organizer
      Bio tech 2012 アカデミックフォーラム
    • Place of Presentation
      東京ビッグサイト
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] アミロイドβのアミロイド化と細胞死に対するGAPDHアミロイド様線維の増強効果2011

    • Author(s)
      瀬見優子、中嶋秀満、久保岳也、板倉正典、東 泰孝、竹内正吉
    • Organizer
      第64回日本薬理学会西南部会
    • Place of Presentation
      福岡(口頭発表)
    • Year and Date
      2011-11-20
    • Related Report
      2012 Final Research Report
  • [Presentation] 新型siRNAのラット側脳室内単回投与によるin vivo脳内蛋白質ノックダウンの有用性2011

    • Author(s)
      久保岳也、中嶋秀満、桑村 充、井澤武史、東 泰孝、竹内正吉
    • Organizer
      第64回日本薬理学会西南部会
    • Place of Presentation
      福岡(口頭発表)
    • Year and Date
      2011-11-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Accell siRNAの単回脳室内投与による脳内の遺伝子サイレンシング効果2011

    • Author(s)
      久保岳也、中嶋秀満、瀬見優子、桑村 充、井澤武史、東 泰孝、竹内正吉
    • Organizer
      第54回日本神経化学会大会
    • Place of Presentation
      加賀(口頭発表)
    • Year and Date
      2011-09-27
    • Related Report
      2012 Final Research Report
  • [Presentation] GAPDH凝集物はアミロイドβの線維化を促進する2011

    • Author(s)
      瀬見優子、中嶋秀満、久保岳也、板倉正典、東 泰孝、竹内正吉
    • Organizer
      第54回日本神経化学会大会
    • Place of Presentation
      加賀(口頭発表)
    • Year and Date
      2011-09-27
    • Related Report
      2012 Final Research Report
  • [Presentation] AccellTMsiRNA のラット側脳室内投与による脳内遺伝子発現のサイレンシング2011

    • Author(s)
      久保岳也、中嶋秀満、桑村 充、井澤武史、東 泰孝、竹内正吉
    • Organizer
      第152回日本獣医学会学術集会
    • Place of Presentation
      堺(口頭発表)
    • Year and Date
      2011-09-20
    • Related Report
      2012 Final Research Report
  • [Presentation] GAPDHアミロイド様線維はアミロイドβの凝集を促進する2011

    • Author(s)
      瀬見優子、中嶋秀満、久保岳也、板倉正典、東 泰孝、竹内正吉
    • Organizer
      第152回日本獣医学会学術集会
    • Place of Presentation
      堺(口頭発表)
    • Year and Date
      2011-09-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Accel ITM siRNAのラット側脳室内投与による脳内遺伝子発現のサイレンシング2011

    • Author(s)
      久保岳也、中嶋秀満、桑村充、井澤武史、東泰孝、竹内正吉
    • Organizer
      第152回日本獣医学会学術集会
    • Place of Presentation
      大阪府立大学(堺市)
    • Year and Date
      2011-09-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] 多機能性酵素GAPDHの脳神経疾患における機能的役割と創薬ターゲットとしての可能性2011

    • Author(s)
      中嶋秀満
    • Organizer
      大阪府立大学メディカルバイオフォーラム
    • Place of Presentation
      泉佐野(口頭発表)
    • Year and Date
      2011-01-29
    • Related Report
      2012 Final Research Report
  • [Presentation] GAPDH とASK1 の機能的相互作用2010

    • Author(s)
      三崎翔平、中嶋秀満、東 泰孝、一條秀憲、竹内正吉
    • Organizer
      第118回日本薬理学会近畿部会
    • Place of Presentation
      豊中(口頭発表)
    • Year and Date
      2010-11-19
    • Related Report
      2012 Final Research Report
  • [Presentation] 多機能性酵素GAPDHの神経細胞死における機能的役割と創薬標的としての可能性2010

    • Author(s)
      中鵡秀満
    • Organizer
      創薬薬理フォーラム第18回シンポジウム「神経細胞保護」
    • Place of Presentation
      東京
    • Year and Date
      2010-09-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] GAPDHアミロイド様繊維とα-synucleinのクロストークと神経細胞死2010

    • Author(s)
      久保岳也、瀬見優子、中嶋秀満、田島久男、東 泰孝、竹内 正吉
    • Organizer
      第150回日本獣医学会学術集会
    • Place of Presentation
      帯広(口頭発表)
    • Year and Date
      2010-09-16
    • Related Report
      2012 Final Research Report
  • [Presentation] 新規酸化ストレスカスケード:GAPDH-ASK1経路の病態生理学的意義の解明2010

    • Author(s)
      三崎翔平、中嶋秀満、東 泰孝、竹内正吉
    • Organizer
      第150回日本獣医学会学術集会
    • Place of Presentation
      帯広(口頭発表)
    • Year and Date
      2010-09-16
    • Related Report
      2012 Final Research Report
  • [Presentation] GAPDH凝集特異的ドミナントネガティブ分子による酸化ストレス誘導性神経細胞死の抑制2010

    • Author(s)
      久保岳也、中嶋秀満、東 泰孝、竹内正吉
    • Organizer
      Neuro2010(第33回日本神経科学大会第53回日本神経化学会大会第20回日本神経回路学会大会合同大会)
    • Place of Presentation
      神戸(口頭発表)
    • Year and Date
      2010-09-02
    • Related Report
      2012 Final Research Report
  • [Presentation] 多機能性酵素GAPDHの神経細胞死における機能的役割と創薬標的としての可能性2010

    • Author(s)
      中嶋秀満
    • Organizer
      創薬薬理フォーラム第18回シンポジウム「神経細胞保護」
    • Place of Presentation
      東京(口頭発表)
    • Year and Date
      2010-02-17
    • Related Report
      2012 Final Research Report
  • [Book] 解糖系酵素glyceraldehyde-3-phosphate dehydrogenase (GAPDH)の多機能性と酸化ストレス性細胞死における役割2010

    • Author(s)
      中嶋秀満、東泰孝、竹内正吉
    • Total Pages
      12
    • Publisher
      放射線生物研究
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.vet.osakafu-u.ac.jp/pham/pham.htm

    • Related Report
      2012 Final Research Report
  • [Remarks] http://www.vet.osakafu-u.ac.jp/pham/pham.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.vet.osakafu-u.ac.jp/pham/pham.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.vet.osakafu-u.ac.jp/pham/pham.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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