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Development of RNA aptamer against toxic Aβ oligomer

Research Project

Project/Area Number 22603006
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field ケミカルバイオロジー
Research InstitutionKyoto University

Principal Investigator

MURAKAMI Kazuma  京都大学, 大学院・農学研究科, 助教 (80571281)

Research Collaborator SHIMIZU Takahiko  千葉大学, 大学院・医学研究院, 客員准教授 (40301791)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsアルツハイマー病 / アミロイド β / 凝集 / オリゴマー / アプタマー / RNA / アミロイドβ / 核酸アプタマー / ジアミノピペリン酸 / Huisgen反応 / 白金 / プロドラッグ / フイスゲン反応 / アジド / アルキン / 細胞質SOD / スーパーオキシドラジカル / 光親和性標識 / ラジカル / 酸化ストレス / ビタミンC / インスリン受容体
Research Abstract

Amyloid β-protein (Aβ), a causative agent of Alzheimer’s disease, aggregates and shows neurotoxicity. It has been well documented that Aβ oligomer (toxic dimer) is mostly related to the neurotoxicity. We have demonstrated that the formation of turn structure at position 22 and 23 plays a critical role in the oligomerization of Aβ. However, it is quite difficult to synthesize Aβoligomer due to the potent ability of Aβ to aggregate. To develop RNA apatamer against toxic Aβdimer, we synthesized Aβ40 dimer, in which Ala30 was substituted with diaminopimelic used as anintermolecular linker. The development of aptamer against Aβ40 dimer is under way.

Report

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

    (30 results)

All 2013 2012 2011 2010 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (14 results) Book (2 results) Remarks (6 results)

  • [Journal Article] Development of a platinum complex as an anti-amyloid agent for the therapy of Alzheimer's disease2013

    • Author(s)
      Vijaya B. Kenche
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 52 Issue: 12 Pages: 3374-3378

    • DOI

      10.1002/anie.201209885

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preparation of stable amyloid β-protein oligomers of defined assembly order2012

    • Author(s)
      Clark Rosensweig, 他5名
    • Journal Title

      Methods in Molecular Biology

      Volume: 489 Pages: 23-31

    • DOI

      10.1007/978-1-61779-551-0_3

    • ISBN
      9781617795503, 9781617795510
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stimulation of the Amyloidogenic Pathway by Cytoplasmic Superoxide Radicals in an Alzheimer's Disease Mouse Model2012

    • Author(s)
      Murakami, K., Murata, N., Noda, Y., Irie, K., Shirasawa, T., Shimizu, T
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 76 Issue: 6 Pages: 1098-1103

    • DOI

      10.1271/bbb.110934

    • NAID

      10030817824

    • ISSN
      0916-8451, 1347-6947
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytoplasmic superoxide radicals as contributing factors to intracellular Aβ oligomerization in Alzheimer's disease2012

    • Author(s)
      Kazuma Murakami, 他1名
    • Journal Title

      Communicative & Integrative Biology

      Volume: 5(3)(印刷中)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SOD1 (cupper/zinc superoxide dismutase) deficiency drives amyloid β protein oligomerization and memory loss in mouse model of Alzheimer's disease2011

    • Author(s)
      Murakami, K., (他8名), Irie, K., Shirasawa, T., Shimizu, T
    • Journal Title

      J. Biol. Chem

      Volume: 286 Issue: 52 Pages: 44557-44568

    • DOI

      10.1074/jbc.m111.279208

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formation of the 42-mer amyloid β radical and the therapeutic role of superoxide dismutase in Alzheimer's disease2011

    • Author(s)
      Kazuma Murakami
    • Journal Title

      Journal of Amino Acids

      Volume: 2011

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vitamin C restores behavioral deficits and Aβ oligomerization without affecting plaque formation in a mouse model of Alzheimer's disease2011

    • Author(s)
      Kazuma Murakami
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insulin receptor mutation results in insulin resistance and hyperinsulinemia but does not exacerbate Alzheimer's-like phenotypes in mice2011

    • Author(s)
      Kazuma Murakami
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 細胞質酸化ストレスによるアミロイドβオリゴマー形成能および記憶異常の促進2012

    • Author(s)
      村上一馬
    • Organizer
      日本農芸化学会2012年度大会
    • Place of Presentation
      京都女子大学
    • Year and Date
      2012-03-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] インスリン抵抗性による高インスリン血症はアルツハイマー病様症状を増悪しない2012

    • Author(s)
      清水孝彦
    • Organizer
      日本農芸化学会2012年度大会
    • Place of Presentation
      京都女子大学
    • Year and Date
      2012-03-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] Insulin receptor mutation results in insulin resistance and hyperinsulinemia but does not worsen Alzheimer's-like phenotypes in mice2011

    • Author(s)
      小澤裕介
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2011-12-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] Insulin receptor mutation results in insulin resistance and hyperinsulinemia but does not exacerbate Alzheimer's-like phenotypes in mice2011

    • Author(s)
      Takuji Shirasawa
    • Organizer
      41st Annual Meeting of Society for Neuroscience
    • Place of Presentation
      Convention Center(Washington,米国)
    • Year and Date
      2011-11-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] 大阪変異によるアミロイドβの毒性コンホマー形成能の増大2011

    • Author(s)
      村上一馬
    • Organizer
      第30回日本認知症学会学術集会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2011-11-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] 抗酸化ストレスに着目したアルツハイマー病予防の可能性2011

    • Author(s)
      村上一馬
    • Organizer
      京都大学原子炉実験所専門研究会「タンパク質の異常凝集とフォールディング病」
    • Place of Presentation
      京都大学原子炉実験所(大阪)(招待講演)
    • Year and Date
      2011-11-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] アミロイドβ異常凝集における「折れ曲がり」の役割2010

    • Author(s)
      村上一馬
    • Organizer
      京都大学原子炉実験所専門研究会「タンパク質の異常凝集とフォールディング病」
    • Place of Presentation
      京都大学原子炉実験所(大阪)
    • Year and Date
      2010-11-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] アルツハイマー病と機能性食品因子(Alzheimer's disease and functional foods)2010

    • Author(s)
      Kazuma Murakami
    • Organizer
      Invited Lecturer in Gwangju University
    • Place of Presentation
      Gwangju大学(Gwangju,韓国)
    • Year and Date
      2010-10-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] Structural analysis of toxic conformer of 42-mer amyloid β peptide using ESR spectrometry2010

    • Author(s)
      Kazuma Murakami
    • Organizer
      7^<th> Asia-Pacific EPR/ESR Symposium
    • Place of Presentation
      Convention Center(Jeju,韓国)
    • Year and Date
      2010-10-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] SOD1の減少はアルツハイマー病様病態を早期に発症させる

    • Author(s)
      清水孝彦
    • Organizer
      第12回日本抗加齢医学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] アミロイド β ペプチドの毒性ターン構造の同定とその構造特異抗体の開発

    • Author(s)
      村上一馬
    • Organizer
      第47回天然物化学談話会
    • Place of Presentation
      阿蘇プラザホテル(熊本)
    • Related Report
      2012 Annual Research Report
  • [Presentation] CuZn-SOD loss accelerates the formation of amyloid β oligomer and memory impairment in Tg2576 mice

    • Author(s)
      Kazuma Murakami
    • Organizer
      Alzheimer's Association International Conference
    • Place of Presentation
      Vancouver Convention Center (Canada)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 酸化ストレスに着目したアミロイドβペプチドの神経細胞毒性発現機構

    • Author(s)
      村上一馬
    • Organizer
      農芸化学奨励賞受賞講演
    • Place of Presentation
      電力ホール(仙台)
    • Related Report
      2012 Annual Research Report
  • [Presentation] ビタミンCにおるアルツハイマー病態緩和

    • Author(s)
      村上一馬
    • Organizer
      2013年度日本農芸化学会大会
    • Place of Presentation
      東北大学川内北キャンパス(仙台)
    • Related Report
      2012 Annual Research Report
  • [Book] タンパク質の異常凝集とその防御・修復機構に関する研究会報告(IV)2011

    • Author(s)
      村上一馬
    • Total Pages
      5
    • Publisher
      京都大学原子炉実験所
    • Related Report
      2011 Annual Research Report
  • [Book] タンパク質の異常凝集とその防御・修復機構に関する研究会報告(III)2010

    • Author(s)
      村上一馬
    • Total Pages
      5
    • Publisher
      アミロイドβ異常凝集における「折れ曲がり」の役割
    • Related Report
      2010 Annual Research Report
  • [Remarks] 京都大学大学院農学研究科食品生物科学専攻生命有機化学分野ホームページ

    • Related Report
      2012 Final Research Report
  • [Remarks] 京都大学教育研究活動データベース

    • Related Report
      2012 Final Research Report
  • [Remarks] 京都大学教育研究活動データベース

    • URL

      http://kyouindb.iimc.kyoto-u.ac.jp/j/zP8kX

    • Related Report
      2012 Annual Research Report
  • [Remarks] 京都大学大学院農学研究科食品生物科学専攻生命有機化学分野ホームページ

    • URL

      http://www.orgchem.kais.kyoto-u.ac.jp/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.orgchem.kais.kyoto-u.ac.jp/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.orgchem.kais.kyoto-u.ac.jp/

    • Related Report
      2010 Annual Research Report

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

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