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The neuroprotective mechanism of lipoproteins for optic nerve degeneration.

Research Project

Project/Area Number 18K07376
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

Hideki Hayashi  東京薬科大学, 薬学部, 准教授 (90508657)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsリポタンパク質 / 神経保護 / 緑内障 / グリア細胞 / アポリポタンパク質E含有リポタンパク質 / LRP1 / 神経保護、 / アルファ2マクログロブリン / リポタンパク質受容体 / 視神経変性
Outline of Final Research Achievements

Glaucoma is a progressive neurodegenerative disease in which the optic nerve is damaged and visual field defect is induced. In the previous study, we showed that alpha 2 macroglobulin (a2M) acts as an interfering factor in the optic nerve protective effect of glia-derived apolipoprotein E-containing lipoproteins (E-LP). In this study, we elucidated the mechanism by which E-LP suppresses a2M expression in retinal glia, and it is possible to provide an environment in which E-LP can indirectly exert the optic nerve protective effect by reducing this interfering factor a2M.

Academic Significance and Societal Importance of the Research Achievements

本研究では、視覚障害原因疾患第1位の緑内障に対し、眼圧降下薬以外の治療薬の開発を目的としてグリア細胞由来アポリポタンパク質E含有リポタンパク質(E-LP)の視神経保護効果に着目した。以前の研究で明らかにしたE-LPの直接的な視神経保護効果に加え、本研究成果ではE-LPがグリア細胞に対し妨害因子を抑制することで視神経保護効果を発揮しやすい環境を整えている可能性を示した。本成果を発展させることによりE-LPの視神経保護機構を利用した新たな緑内障治療薬の開発研究が進展することを期待する。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (17 results)

All 2021 2020 2019 2018 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (13 results) (of which Int'l Joint Research: 4 results) Remarks (1 results)

  • [Journal Article] Effects of laminin-111 peptide coatings on rat neural stem/progenitor cell culture.2021

    • Author(s)
      Hayashi H, Horinokita I, Yamada Y, Hamada K, Takagi N, Nomizu M.
    • Journal Title

      Experimental Cell Research

      Volume: 400 Issue: 1 Pages: 112440-112440

    • DOI

      10.1016/j.yexcr.2020.112440

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigating the Relationship Between Neuronal Cell Death and Early DNA Methylation After Ischemic Injury.2020

    • Author(s)
      Asada M, Hayashi H, Murakami K, Kikuiri K, Kaneko R, Yuan B, Takagi N.
    • Journal Title

      Frontiers in Neuroscience

      Volume: 14 Pages: 581915-581915

    • DOI

      10.3389/fnins.2020.581915

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Furin-mediated cleavage of LRP1 and increase in ICD of LRP1 after cerebral ischemia and after exposure of cultured neurons to NMDA2019

    • Author(s)
      Yamada Mariko、Hayashi Hideki、Suzuki Kaori、Sato Shoko、Inoue Daisuke、Iwatani Yui、Ohata Meiko、Yuan Bo、Takagi Norio
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 11782-11782

    • DOI

      10.1038/s41598-019-48279-x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 虚血性神経障害における DNA メチル化の役割2021

    • Author(s)
      浅田 眞由美、林 秀樹、村上 健二郎、菊入 健斗、金子 遼太郎、袁 博、高木 教夫
    • Organizer
      第94回 日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] リポタンパク質受容体LRP1シグナルによる視神経保護2020

    • Author(s)
      林 秀樹、高木 教夫
    • Organizer
      第63回 日本神経化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] グリア細胞由来リポタンパク質のLRP1を介した神経保護と緑内障治療への応用2020

    • Author(s)
      林 秀樹、高木 教夫
    • Organizer
      第93回 日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Neuroprotective roles of apolipoprotein E containing lipoproteins in neurons and glia of retina2019

    • Author(s)
      H. Hayashi, M. Mori, M. Yamada, B. Yuan, N. Takagi
    • Organizer
      Neuroscience 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] アポE含有リポタンパク質による初代培養網膜グリア細胞のα2マクログロブリン発現調節機構の解析2019

    • Author(s)
      竹村映美、林 秀樹、向垣内千早、袁 博、高木 教夫
    • Organizer
      第140回 日本薬理学会関東部会
    • Related Report
      2019 Research-status Report
  • [Presentation] 虚血性脳神経障害時のLRP1プロセシングと神経細胞死の関連2019

    • Author(s)
      今村唯、堀之北一朗、林 秀樹、高木 教夫
    • Organizer
      第140回 日本薬理学会関東部会
    • Related Report
      2019 Research-status Report
  • [Presentation] 網膜のリポタンパク質受容体LRP1と視神経生存2019

    • Author(s)
      林 秀樹、森 みすず、原嶋美奈、橋爪達哉、向垣内千早、山田まりこ、袁 博、高木教夫
    • Organizer
      第42回 日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Apo E-containing lipoproteins protect retinal ganglion cells from glaucomatous optic neuropathy via an LRP1-mediated pathway2018

    • Author(s)
      Hideki Hayashi, Misuzu Mori, Mariko Yamada, Bo Yuan, Norio Takagi
    • Organizer
      59th International Conference on the Bioscience of Lipids
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] A possible neuroprotective mechanism of preventing LRP1 cleavage after ischemic brain damage2018

    • Author(s)
      Mariko Yamada, Hideki Hayashi, Yui Iwatani, Kaori Suzuki, Bo Yuan, Norio Takagi
    • Organizer
      59th International Conference on the Bioscience of Lipids
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Protective effects of apolipoprotein E-containing lipoproteins against glaucomatous optic neuropathy2018

    • Author(s)
      Hideki Hayashi, Mariko Yamada, Misuzu Mori, Mio Kobayashi, Hikaru Koide, Takuya Kojima, Chihaya Mukaigaito, Bo Yuan, Norio Takagi
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Roles of low density lipoprotein receptor-related protein 1 ligands in glaucomatous optic neuropathy2018

    • Author(s)
      Hideki Hayashi, Misuzu Mori, Mariko Yamada, Bo Yuan, Norio Takagi
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ラット緑内障モデルのアポE含有リポタンパク質による視神経保護とα2-マクログロブリンの働き2018

    • Author(s)
      林 秀樹、森 みすず、山田 まりこ、袁 博、高木 教夫
    • Organizer
      第60回 日本脂質生化学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 虚血性脳神経障害時の LRP1 プロセシングと神経生存2018

    • Author(s)
      山田 まりこ、林 秀樹、井上 大輔、大畑 芽衣子、松嶋 菜穂子、袁 博、高木 教夫
    • Organizer
      第60回 日本脂質生化学会
    • Related Report
      2018 Research-status Report
  • [Remarks] 東京薬科大学応用生化学教室ホームページ

    • URL

      https://www.ps.toyaku.ac.jp/ouyoseika/

    • Related Report
      2020 Annual Research Report 2019 Research-status Report 2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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