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Development of in vitro amyloid fibril formation systems that mimic the physiological fibrillogenesis conditions in vivo

Research Project

Project/Area Number 24570129
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Structural biochemistry
Research InstitutionUniversity of Fukui

Principal Investigator

HASEGAWA Kazuhiro  福井大学, 医学部, 助教 (60324159)

Co-Investigator(Kenkyū-buntansha) NAIKI Hironobu  福井大学, 医学部, 教授 (10227704)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords蛋白質 / 脳神経疾患 / 病理学 / アミロイド / アルツハイマー病
Outline of Final Research Achievements

We constructed several amyloid fibril formation systems in vitro to evaluate the roles of the various biological molecules or reaction conditions in the amyloid fibril formation. The key findings of this study are as follows: (1) We developed a near-physiological Alzheimer's disease amyloid β-peptide (Aβ) fibril formation system for evaluating the efficiency of protein components to induce the nucleation of Aβ-peptide. To suppress spontaneous Aβ nucleation, the system includes protein coated Sepharose beads and low concentration of Aβ peptide solution without air in the reaction vessel. Using the system, we indicated several basement membrane components accelerate Aβ fibril formation in vitro. (2) To further decrease the concentration of Aβ peptide in the reaction, we are developing an open flow system, where near physiological concentrations of Aβ peptide are continuously supplied to the reaction surface.

Report

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

    (11 results)

All 2015 2014 2013 2012

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (8 results)

  • [Journal Article] C-terminal sequence of amyloid-resistant type F apolipoprotein A-II inhibits amyloid fibril formation of apolipoprotein A-II in mice.2015

    • Author(s)
      J.Sawashita, B.Zhang, K.Hasegawa, M.Mori, H.Naiki, F.Kametani, K.Higuchi.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 112 Issue: 8

    • DOI

      10.1073/pnas.1416363112

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ヒトアミロイド線維形成・沈着の分子機構2014

    • Author(s)
      内木 宏延, 長谷川 一浩, 小澤 大作, 大越 忠和
    • Journal Title

      Dementia Japan

      Volume: 28 Pages: 275-282

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Surface-bound basement membrane components accelerate amyloid-β peptide nucleation in air-free wells: An in vitro model of cerebral amyloid angiopathy.2013

    • Author(s)
      Hasegawa K, Ozawa D, Ookoshi T, Naiki H
    • Journal Title

      Biochim Biophys Acta

      Volume: 1834 Issue: 8 Pages: 1624-1631

    • DOI

      10.1016/j.bbapap.2013.04.011

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 滑膜線維芽細胞に対するβ2-ミクログロブリンアミロイド線維の細胞毒性メカニズムの解析2014

    • Author(s)
      大越 忠和, 山口 格, 小澤 大作, 長谷川 一浩, 内木 宏延
    • Organizer
      第 2 回日本アミロイドーシス研究会学術集会
    • Place of Presentation
      KKRホテル東京 (東京都千代田区)
    • Year and Date
      2014-08-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] A novel cytotoxic mechanism of amyloid fibrils: Endocytosis-dependent necrosis and apoptosis of rabbit synovial fibroblasts by β2-microglobulin amyloid fibrils.2014

    • Author(s)
      T.Ookoshi, D.Ozawa, K.Hasegawa, H.Naiki
    • Organizer
      XIVth International Symposium on Amyloidosis
    • Place of Presentation
      Indianapolis (USA)
    • Year and Date
      2014-04-27 – 2014-05-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] β2-ミクログロブリンアミロイド線維は滑膜線維芽細胞内に取り込まれ毒性を発揮する-形態解析を中心に-2014

    • Author(s)
      大越 忠和, 長谷川 一浩, 小澤 大作, 内木 宏延
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場 (広島市)
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] ビーズ表面に結合した細胞外マトリクス成分は、気液界面非存在下でアルツハイマー病βアミロイド線維の核形成を促進させる2013

    • Author(s)
      長谷川 一浩, 小澤 大作, 大越 忠和, 内木 宏延
    • Organizer
      日本生物物理学会第51回年会
    • Place of Presentation
      京都, 京都国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] β2-ミクログロブリンアミロイド線維の線維芽滑膜細胞に対する細胞毒性の検討2013

    • Author(s)
      大越 忠和, 長谷川 一浩, 小澤 大作, 内木 宏延
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌, ロイトン札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] Molecular mechanisms of β2-microglobulin amyloid fibril formation.2012

    • Author(s)
      Ozawa D, Hasegawa K, Ookoshi T, Naiki H
    • Organizer
      XIIIth International Symposium on Amyloidosis
    • Place of Presentation
      Groningen(the Netherlands)
    • Related Report
      2012 Research-status Report
  • [Presentation] 細胞外シャペロンによるアミロイド線維形成抑制機構の解明2012

    • Author(s)
      小澤大作, 長谷川一浩, 李 映昊, 櫻井一正, 柳 浩太郎, 大越忠和, 後藤祐児, 内木宏延
    • Organizer
      第12回日本蛋白質科学会年会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] マウスF型apoA-IIのC末ペプチドは老化アミロイドーシス高発症マウスのアミロイド沈着を軽減する2012

    • Author(s)
      澤下仁子, 他
    • Organizer
      第27回老化促進モデルマウス(SAM)研究協議会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report

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

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