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Anti-Alzheimer's disease effect by inhibition of prion protein which is an Ab receptor by RNA

Research Project

Project/Area Number 20K21477
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionKyoto University

Principal Investigator

Katahira Masato  京都大学, エネルギー理工学研究所, 教授 (70211844)

Project Period (FY) 2020-07-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywordsアルツハイマー病 / プリオン蛋白質 / アミロイドβ / RNAアプタマー / アプタマー / 4重鎖 / プリオン / 相互作用 / 抗アルツハイマー病 / プリオンタンパク質 / Aβタンパク質 / LTP / Aβ
Outline of Research at the Start

神経細胞の表面のプリオン蛋白質(PrP)は、オリゴマー化したアミロイドβ(Aβ)蛋白質の受容体として機能し、アルツハイマー病と密接に関連するAβオリゴマーの病因性シグナルを細胞内に伝達する事が報告された。PrPに対する抗体でPrPをマスクして受容体として機能できないようにすると、Aβオリゴマーの病因性シグナルは、細胞内に伝達されない事も報告された。本研究では抗体ではなく、PrPに高い親和性で結合するRNA分子(RNAアプタマー)を用い、これによってPrPをマスクする事でPrPが受容体として機能できないようにし、Aβオリゴマーの病因性シグナルが細胞内に伝達するのを阻害する事を試みる。

Outline of Final Research Achievements

It was reported that prion protein (PrP) functions as a receptor of oligomerized amyloid b protein (Ab), which is related to Alzheimers’s disease, and transmits a pathological signal into cells. We attempted to mask PrP by an RMA aptamer toward PrP and thus block the transmission of the pathological signal. Collaborative study with Professors Mori and Nakao, Kyoto University, implied that the RNA aptamer could repress the transmission of the signal.

Academic Significance and Societal Importance of the Research Achievements

アミロイドβ(Aβ)蛋白質の病因性シグナルが、細胞表面の受容体であるプリオンタンパク質を介して細胞内に伝達される事を、プリオンタンパク質に対するRNAアプタマーによって遮断できる事が示唆されたことは、アルツハイマー病の治療に向けた新たな基盤となる可能性を有する新知見であり、学術的及び社会的に意義がある。

Report

(3 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (11 results)

All 2021 2020 Other

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

  • [Int'l Joint Research] Gyeongsang National University(韓国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Investigation of the Interaction of Human Origin Recognition Complex Subunit 1 with G-Quadruplex DNAs of Human c-myc Promoter and Telomere Regions2021

    • Author(s)
      Eladl Afaf、Yamaoki Yudai、Hoshina Shoko、Horinouchi Haruka、Kondo Keiko、Waga Shou、Nagata Takashi、Katahira Masato
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 7 Pages: 3481-3481

    • DOI

      10.3390/ijms22073481

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Investigation of the interaction of human origin recognition complex subunit 1 with G-quadruplex DNAs of human c-myc promoter and telomere regions2021

    • Author(s)
      Eladl, A., Yamaoki, Y., Hoshina, S., Horinouchi, H., Kondo, K., Waga, S., Nagata, T., Katahira, M.
    • Journal Title

      Int. J. Mol. Sci.

      Volume: -

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development and structural determination of an anti-PrPC aptamer that blocks pathological conformational conversion of prion protein2020

    • Author(s)
      Mashima Tsukasa、Lee Joon-Hwa、Kamatari Yuji O.、Hayashi Tomohiko、Nagata Takashi、Nishikawa Fumiko、Nishikawa Satoshi、Kinoshita Masahiro、Kuwata Kazuo、Katahira Masato
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 4934-4934

    • DOI

      10.1038/s41598-020-61966-4

    • NAID

      120006813315

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Direct visualization of the conformational change of FUS/TLS upon binding to promoter-associated non-coding RNA2020

    • Author(s)
      Nesreen Hamad, Hiroki Watanabe, Takayuki Uchihashi, Riki Kurokawa, Takashi Nagata, and Masato Katahira
    • Journal Title

      Chemical Communications

      Volume: 56 Issue: 64 Pages: 9134-9137

    • DOI

      10.1039/d0cc03776a

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Quadruplex RNA aptamers with anti-disease activities and in-cell NMR of nucleic acids2021

    • Author(s)
      Katahira, M.
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] RNAアプタマーの構造・抗プリオン活性・抗アミロイドβ活性及びヒト細胞中における核酸のin-cell NMR2021

    • Author(s)
      片平正人
    • Organizer
      日本農芸化学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Study of the interaction between human origin recognition complex subunit 1 and G-quadruplex forming nucleic acids2021

    • Author(s)
      Eladl, A., Yamaoki, Y., Hoshina, S., Horinouchi, H., Kondo, K., Waga, S., Nagata, T. and Katahira, M.
    • Organizer
      22nd International Society of Magnetic Resonance Conference
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Human origin recognition complex subunit 1 bound to DNAs that form G-quadruplex structures2021

    • Author(s)
      Waga, S., Yamaoki, Y., Eladl, A., Hoshina, S., Horinouchi, H., Kondo, K., Nagata, T. and Katahira, M.
    • Organizer
      The 12th International Symposium of Advanced Energy Science
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抗プリオン病・抗アルツハイマー病効果が期待されるRNA分子の構造・機能研究とin-cell NMR2021

    • Author(s)
      片平正人
    • Organizer
      日本分光学会NMR分光部会集中講義
    • Related Report
      2021 Research-status Report
    • Invited
  • [Remarks] 片平研究室

    • URL

      http://www.iae.kyoto-u.ac.jp/bio/

    • Related Report
      2021 Research-status Report 2020 Research-status Report

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Published: 2020-08-03   Modified: 2024-12-25  

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