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Analysis of the mechanism of exacerbation of neurodegeneration by innate immunity

Research Project

Project/Area Number 19K06445
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42030:Animal life science-related
Research InstitutionRikkyo University

Principal Investigator

Goto Satoshi  立教大学, 理学部, 教授 (60280575)

Co-Investigator(Kenkyū-buntansha) 山本 美紀 (日野美紀)  立教大学, 理学部, 助教 (40301783)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords神経変性 / D-knif family / 免疫 / 神経 / ショウジョウバエ
Outline of Research at the Start

自然免疫はほとんどの多細胞生物が有する生体防御機構である。私達は自然免疫が神経変性を増悪化することを見出したので、本研究ではそのメカニズムを明らかにすることを目指す。そのために、自然免疫の活性化が、神経変性の進行において、どのような影響を与えているかを明らかにする。次に、影響のあったステップに関与するシグナル経路を明らかにする。さらに、その上流にある受容体を明らかにする。最後に、明らかになった経路、受容体が実際にin vivoでも役割を果たしているかについてモデル生物を用いて検討する。以上のことにより、神経変性における自然免疫の影響のメカニズムの一端が明らかになるだろう。

Outline of Final Research Achievements

Living organisms have an innate defense response called innate immunity to protect themselves from various pathogens. Recently, it has been shown that innate immunity is activated not only during infection but also in neurodegenerative diseases, but it is not well understood whether the activation of innate immunity is involved in the progression of neurodegeneration. Using a fly model of neurodegenerative disease, we have shown that a molecule induced during innate immune activation acts in a pro-neurodegenerative manner, and we have named this molecule D-knif. In this study, we investigated whether the same phenomenon is observed in mammals and the effect of the human D-knif family on human neurons, and were able to show that the D-knif family molecules also act to promote neurodegeneration in humans.

Academic Significance and Societal Importance of the Research Achievements

すべての多細胞生物に備わる自然免疫システムは生体防御を実行する。しかし、神経変性の過程においても自然免疫が活性化する。私達はショウジョウバエを用い、その自然免疫の活性化は神経変性を増悪化することをも見出した。さらに、それがショウジョウバエに留まらず哺乳動物でも保存されているかを検討し、培養細胞レベルで保存されていることを見出した。本研究の成果は、ヒトにおける神経変性疾患の理解に貢献する。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (9 results)

All 2021 2020 2019

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (5 results) (of which Invited: 1 results)

  • [Journal Article] Subunits of the GPI transamidase complex localize to the endoplasmic reticulum and nuclear envelope in Drosophila2021

    • Author(s)
      Kawaguchi Kohei、Yamamoto‐Hino Miki、Matsuyama Nina、Suzuki Emiko、Goto Satoshi
    • Journal Title

      FEBS Letters

      Volume: 595 Issue: 7 Pages: 960-968

    • DOI

      10.1002/1873-3468.14048

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hrd1-dependent Degradation of the Unassembled PIGK Subunit of the GPI Transamidase Complex2021

    • Author(s)
      Kawaguchi Kohei、Yamamoto-Hino Miki、Murakami Yoshiko、Kinoshita Taroh、Goto Satoshi
    • Journal Title

      Cell Structure and Function

      Volume: 46 Issue: 2 Pages: 65-71

    • DOI

      10.1247/csf.21019

    • NAID

      130008083701

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SPPL3-dependent downregulation of the synthesis of (neo)lacto-series glycosphingolipid is required for the staining of cell surface CD592021

    • Author(s)
      Kawaguchi Kohei、Yamamoto-Hino Miki、Goto Satoshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 571 Pages: 81-87

    • DOI

      10.1016/j.bbrc.2021.06.093

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lamin is essential for nuclear localization of the GPI synthesis enzyme PIG-B and GPI-anchored protein production in Drosophila2020

    • Author(s)
      Yamamoto-Hino Miki、Kawaguchi Kohei、Ono Masaya、Furukawa Kazuhiro、Goto Satoshi
    • Journal Title

      Journal of Cell Science

      Volume: 133 Issue: 6 Pages: 238527-238527

    • DOI

      10.1242/jcs.238527

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 核ラミンの均一なメッシュワークの形成とその機能2021

    • Author(s)
      後藤 聡, 山本(日野) 美紀
    • Organizer
      第44回 日本分子生物学会年会 ワークショップ
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] An organelle zone executing a posttranslational modification of proteins2019

    • Author(s)
      Satoshi Goto, Miki Yamamoto-Hino, Kohei Kawaguchi, Masaya Ono
    • Organizer
      Joint Annual Meeting of the 71th JSCB and 19th PSSJ Workshop
    • Related Report
      2019 Research-status Report
  • [Presentation] GPI修飾ゾーンの解析2019

    • Author(s)
      後藤聡
    • Organizer
      第38回 日本糖質学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Coupling of translation and GPI modification2019

    • Author(s)
      Kohei Kawaguchi, Miki Yamamoto-Hino, Masaya Ono, Yoshiko Murakami, Taroh Kinoshita, Satoshi Goto
    • Organizer
      第42回 日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] GPI修飾を司る翻訳後修飾ゾーン2019

    • Author(s)
      後藤聡、山本(日野)美紀、川口紘平、尾野雅哉、木下タロウ、古川和弘
    • Organizer
      第42回 日本分子生物学会年会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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