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Development of a novel therapeutic strategy for Alzheimer's disease targeting on nicotinic acetylcholine receptors on microglia

Research Project

Project/Area Number 22790090
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

TAKATA Kazuyuki  京都薬科大学, 薬学部, 助教 (10434664)

Research Collaborator 谷口 隆之  京都薬科大学, 教授
下濱 俊  札幌医科大学, 教授
富本 秀和  三重大学, 教授
北村 佳久  京都薬科大学, 准教授
西村 周泰  CiRA, 研究員
ALFRED Maelicke  Galantos, Pharma, CSO
佐伯 真菜  京都薬科大学, 大学院生
寺田 真希  京都薬科大学, 大学院生
鍵谷 沙智子  京都薬科大学, 大学院生
北村 理紗  京都薬科大学, 大学院生
辰田 博則  京都薬科大学, 大学院生
高田 哲也  京都薬科大学, 学部生
藤川 靖浩  京都薬科大学, 学部生
鶴野 友美  京都薬科大学, 学部生
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥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 / ミクログリア / ニコチン性アセチルコリン受容体 / 貪食 / ガランタミン / アロステリック活性化リガンド / 骨髄細胞 / 骨髄幹細胞 / 移植 / macrophage-colony stimulating factor / 再生医療 / allosterically potentiating ligand / トランスジェニックマウス
Research Abstract

Galantamine is an acetylcholinesterase inhibitor approved for symptomatic treatment of Alzheimer's disease. Galantamine also acts as an allosterically potentiating ligand for nicotinic acetylcholine receptors(nAChRs). In this study, we demonstrated that galantamine stimulates nAChRs on microglia and promotes microglial phagocytic ability. This effect resulted in the reduction of amyloid-β burden in the brain which is thought to be a primary pathological event in the development of Alzheimer's disease. We further successfully differentiated bone-marrow cells to the microglia-like amyloid-β phagocytic cells.

Report

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

    (13 results)

All 2012 2011 2010 Other

All Journal Article (5 results) (of which Peer Reviewed: 4 results) Presentation (4 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Molecular approaches to the treatment, prophylaxis, and diagnosis of Alzheimer's disease : tangle formation, amyloid-β, and microglia in Alzheimer's disease2012

    • Author(s)
      Kazuyuki Takata and Yoshihisa Kitamura
    • Journal Title

      J. Pharmacol Sci

      Volume: 188 Pages: 338-344

    • NAID

      10030455494

    • Related Report
      2011 Final Research Report
  • [Journal Article] Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer&rsquo;s Disease:<BR>Tangle Formation, Amyloid-<I>&beta;</I>, and Microglia in Alzheimer&rsquo;s Disease2012

    • Author(s)
      Kazuyuki Takata, et al
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 118 Issue: 3 Pages: 331-337

    • DOI

      10.1254/jphs.11R10FM

    • NAID

      10030455494

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preparation and characterization of microglia-like cells derived from rat, mouse, and human bone marrow cells for therapeutic strategy of Alzheimer's disease2011

    • Author(s)
      Kazuyuki Takata, Tetsuya Takada, Hironori Tatsuda, Tomomi Tsuruno, Kaneyasu Nishimura, Shun Shimohama, and Yoshihisa Kitamura
    • Journal Title

      J. Addict. Res. Ther

      Volume: S5 Pages: 1-5

    • DOI

      10.4172/2155-6105.s5-001

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Galantamine-induced amyloid-β clearance mediated via stimulation of microglial nicotinic acetylcholine receptors2010

    • Author(s)
      Kazuyuki Takata, Yoshihisa Kitamura, Mana Saeki, Maki Terada, Sachiko Kagitani, Risa Kitamura, Yasuhiro Fujikawa, Alfred Maelicke, Hidekazu Tomimoto, Takashi Taniguchi, and Shun Shimohama
    • Journal Title

      J. Biol. Chem

      Volume: 285 Pages: 40180-40191

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Galantamine-induced amyloid-β clearance mediated via stimulation of microglial nicotinic acetylcholine receptors.2010

    • Author(s)
      Kazuyuki Takata, et al.
    • Journal Title

      J.Biol.Chem.

      Volume: 285 Pages: 40180-40191

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Translational research on compensatory microglial function for therapeutic strategy of Alzheimer's disease2011

    • Author(s)
      Kazuyuki Takata and Yoshihisa Kitamura
    • Organizer
      第5回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      名古屋大学医学部附属病院(愛知県)
    • Year and Date
      2011-11-27
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] ガランタミンによるミクログリアのアミロイドβ貪食促進作用2011

    • Author(s)
      高田和幸、北村佳久、谷口隆之
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      ツインメッセ静岡(静岡県)
    • Year and Date
      2011-03-30
    • Related Report
      2011 Final Research Report
  • [Presentation] ガランタミンによるミクログリアのアミロイドβ貪食促進作用2011

    • Author(s)
      高田和幸, 他
    • Organizer
      日本薬学会 第131年会
    • Place of Presentation
      ツインメッセ静岡(静岡県)
    • Year and Date
      2011-03-30
    • Related Report
      2010 Annual Research Report
  • [Presentation] ニコチン性アセチルコリン受容体のアロステリック制御によるミクログリアのアミロイドβ貪食促進作用の解析2011

    • Author(s)
      高田和幸、北村佳久、下濱俊、谷口隆之
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2011-03-23
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Book] Chapter 8 : Microglial functions against amyloid-β accumulation in brains of Alzheimer's disease. Microglia : Biology, Functions and Roles in Disease, Edited by Charanjit Kaur and Ling Eng-Ang2012

    • Author(s)
      Kazuyuki Takata and Yoshihisa Kitamura
    • Publisher
      NOVA Science Publishers(in press)
    • Related Report
      2011 Final Research Report
  • [Book] Chapter 8 : Microglial functions against amyloid-β accumulation in brains of Alzheimer's disease. Microglia : Biology, Functions and Roles in Disease2012

    • Author(s)
      Kazuyuki Takata, et al
    • Publisher
      NOVA Science Publishers(In press)
    • Related Report
      2011 Annual Research Report
  • [Remarks] アルツハイマー治療薬に新たな働きアミロイドベータ除去.京都新聞, 2010年12月21日

    • Related Report
      2011 Final Research Report
  • [Remarks] ガランタミンの新たな作用機序を発見ミクログリアによるAβ除去を促進.薬事日報, 2010年11月17日

    • Related Report
      2011 Final Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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