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Formation and Propagation Mechanism of Prion Protein Oligomers "Watched" by Aggregation-Induced Emission Imaging

Research Project

Project/Area Number 17K07315
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Structural biochemistry
Research InstitutionChiba Institute of Technology

Principal Investigator

Yamamoto Norifumi  千葉工業大学, 工学部, 教授 (30452163)

Co-Investigator(Kenkyū-buntansha) 島崎 俊明  千葉工業大学, 工学部, 准教授 (10452476)
鎌足 雄司  岐阜大学, 高等研究院, 助教 (70342772)
Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsプリオン病 / 凝集誘起発光 / タンパク質 / アミロイド / 蛍光イメージング / プリオンタンパク質 / 蛍光プローブ / 分子イメージング / 分子シミュレーション / イメージング / アルツハイマー病 / シミュレーション / 蛋白質 / 生物物理 / 化学物理 / 脳神経疾患
Outline of Final Research Achievements

In this study, we developed a new fluorescent probe that combines an anti-prion compound and an aggregation-induced emission (AIE) luminogen to "watch" the dynamics of prion protein oligomers in living cells. We confirmed that the fluorescence intensity increased when the developed fluorescent probe interacted with prion oligomers and succeeded in establishing the basis for AIE imaging. Furthermore, to develop new fluorescent probes, we analyzed the AIE process observed with tetraphenylethylene and cyanostilbene derivatives and clarified the molecular mechanism. These advances are expected to contribute to the development of diagnostic and therapeutic methods for diseases caused by "abnormal protein aggregation" such as prion diseases.

Academic Significance and Societal Importance of the Research Achievements

本研究は、抗プリオン化合物に凝集誘起発光特性を付与するという着想を出発点として、これまで観測できなかったPrPオリゴマーを検出する新しい方法論を提案し、プリオン病研究の突破口を切り拓くことで、その診断・治療法開発への貢献が期待できる。プリオン病のみならず、アルツハイマー病においても、アミロイドβオリゴマーが重要な役割を果たすことが明らかになりつつある 。本研究で提案するタンパク質凝集体のイメージング技術をPrP以外のタンパク質に応用することで、有症率の高いアミロイドーシスについても診断・治療法確立を実現する新たな道筋を切り拓くことが可能性となり、保健医療福祉分野への大きな波及効果が期待できる。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2022 2021 2020 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (15 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results)

  • [Journal Article] Janus-Type AIE Fluorophores: Synthesis and Properties of π-Extended Coumarin-Bearing Triskelions2022

    • Author(s)
      Ueda Masafumi、Kokubun Mirai、Yanagi Nao、Yamamoto Norifumi、Mazaki Yasuhiro
    • Journal Title

      Molecules

      Volume: 27 Issue: 21 Pages: 7450-7450

    • DOI

      10.3390/molecules27217450

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Free energy profile analysis to identify factors activating the aggregation-induced emission of a cyanostilbene derivative2021

    • Author(s)
      Norifumi Yamamoto
    • Journal Title

      Phys. Chem. Chem. Phys.

      Volume: 23 Issue: 2 Pages: 1317-1324

    • DOI

      10.1039/d0cp04246c

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Free Energy Profile Analysis for the Aggregation-Induced Emission of Diphenyldibenzofulvene2020

    • Author(s)
      Norifumi Yamamoto
    • Journal Title

      The Journal of Physical Chemistry A

      Volume: - Issue: 24 Pages: 4939-4945

    • DOI

      10.1021/acs.jpca.0c03240

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of Aggregation-Induced Emission and Photo/Thermal E/Z Isomerization of a Cyanostilbene Derivative: Theoretical Insights2018

    • Author(s)
      Norifumi Yamamoto
    • Journal Title

      The Journal of Physical Chemistry C

      Volume: 122 Issue: 23 Pages: 12434-12440

    • DOI

      10.1021/acs.jpcc.8b02147

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Theoretical Insights into the Mechanism of Aggregation-Induced Emission2022

    • Author(s)
      山本 典史
    • Organizer
      化学系学協会東北大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 三脚巴状分子の凝集誘起発光過程に関する自由エネルギープロファイル解析2022

    • Author(s)
      柳 南帆, 上田 将史, 山本 典史
    • Organizer
      第16回 分子科学討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 三脚巴状分子の螺旋反転過程に関する自由エネルギープロファイル解析2022

    • Author(s)
      大場 勇希, 上田 将史, 山本 典史
    • Organizer
      第16回 分子科学討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 凝集誘起発光過程の自由エネルギープロファイル解析2022

    • Author(s)
      山本 典史
    • Organizer
      IQCE 量子化学探索講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] テトラフェニルエチレンの凝集誘起発光過程に関する自由エネルギープロファイル解析2022

    • Author(s)
      酒井 祐輔, 山本 典史
    • Organizer
      第16回 分子科学討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] クマリンを有する三脚巴状分子の凝集誘起発光についての理論的研究2021

    • Author(s)
      柳 南帆, 山本 典史
    • Organizer
      第15回 分子科学討論会, オンライン, ポスター発表, 2P086
    • Related Report
      2021 Research-status Report
  • [Presentation] 三脚巴状分子の凝集誘起発光メカニズムについての理論的研究2021

    • Author(s)
      柳 南帆, 山本 典史
    • Organizer
      日本コンピュータ化学会 2021年 秋季大会, オンライン, ポスター発表, 1P12
    • Related Report
      2021 Research-status Report
  • [Presentation] Theoretical insights into the mechanisms of aggregation-induced emission of a cyanostilbene derivative2021

    • Author(s)
      山本 典史
    • Organizer
      Pacifichem 2021, オンライン, 口頭発表
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Theoretical insights into the mechanisms of aggregation-induced emission (AIE) of a cyanostilbene derivative2019

    • Author(s)
      Norifumi Yamamoto
    • Organizer
      American Chemical Society National Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Theoretical Insights into the Mechanisms of Aggregation-Induced Emission of Tetraphenylethylene2019

    • Author(s)
      Norifumi Yamamoto
    • Organizer
      American Physical Society March Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Theoretical Insights into the Mechanisms of Aggregation-Induced Emission of a Cyanostilbene Derivative2018

    • Author(s)
      Norifumi Yamamoto
    • Organizer
      American Chemical Society National Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Theoretical Insights into Aggregation-Induced Emission of a Cyanostilbene Derivative2018

    • Author(s)
      Norifumi Yamamoto
    • Organizer
      International Conference of Computational Methods in Science and Engineering (ICCMSE)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Theoretical Study on the Aggregation Induced Emission of a Syanostilbene Derivative2018

    • Author(s)
      Norifumi Yamamoto
    • Organizer
      日本化学会春季年会
    • Related Report
      2017 Research-status Report
  • [Presentation] シアノスチルベン誘導体の凝集誘起発光についての理論的研究2017

    • Author(s)
      山本典史
    • Organizer
      分子科学討論会
    • Related Report
      2017 Research-status Report
  • [Presentation] 分子シミュレーションを用いたプリオン形成中間体の解析:プリオン病感染機構の解明を目指して2017

    • Author(s)
      山本典史
    • Organizer
      情報計算化学生物(CBI)学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2024-01-30  

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