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Regulation of retrograde signaling through axonal transport and its role in the onset of Alzheimer's disease

Research Project

Project/Area Number 20K07742
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 InstitutionKanagawa Institute of Technology (2021-2023)
Juntendo University (2020)

Principal Investigator

Naoya YAMASHITA  神奈川工科大学, 応用バイオ科学部, 准教授 (40508793)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords軸索輸送 / 逆行性シグナル / トランスサイトーシス / アルツハイマー病
Outline of Research at the Start

アルツハイマー病(AD)の発症にはアミロイドβ前駆タンパク質(APP)の切断産物であるアミロイドβ(Aβ)が深く関与するが、その過剰産生を引き起こす機構は不明である。研究代表者は、神経成長因子(NGF)とセマフォリン3A(Sema3A)により制御される軸索輸送を介した逆行性シグナルの制御異常が、Aβの過剰産生を引き起こす可能性を見出した。そこで本課題では、NGFとSema3A逆行性シグナルの制御異常がAβの過剰産生を引き起こす機構の解明と、そのAD病態との関係を明らかにするための研究を実施する。

Outline of Final Research Achievements

Alzheimer's disease (AD) is one of the neurodegenerative diseases that we must find a way to cure. Toxic aggregation of amyloid β (Aβ) in neurons is implicated in AD pathology. However, the mechanisms that induce accumulation of Aβ in the brain remain unclear. In this study, we newly identified an axonal transport dependent neuronal signaling that controls Aβ production. Moreover, we found that disruption of this signaling may be related to the onset of AD. Our study therefore provides a basis for predicting and preventing the onset of AD.

Academic Significance and Societal Importance of the Research Achievements

人類がADを克服するためには、その発症の引き金となりうるAβの蓄積を引き起こす要因を明らかにする必要がある。本研究では、軸索輸送と呼ばれる神経細胞の生存に関わる機構の新たな役割を見出した。さらに、発見した機構の破綻がAβ蓄積を引き起こしてAD発症に関わる可能性を突き止めた。従って、本研究には、神経細胞の発達や機能の制御における基本原理の解明にとどまらず、AD発症に関わる新しい機構の発見につながる可能性がある。ここに、得られた成果の学術的意義と社会的意義が存在する。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (15 results)

All 2023 2022 2021 2020

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (10 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Transcytosis-mediated anterograde transport of TrkA receptors is necessary for sympathetic neuron development and function2023

    • Author(s)
      Blaine Connor, Guillermo Moya-Alvarado, Naoya Yamashita, Rejji Kuruvilla
    • Journal Title

      The Proceedings of the National Academy of Sciences

      Volume: 120(6) Issue: 6 Pages: 1-12

    • DOI

      10.1073/pnas.2205426120

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia2021

    • Author(s)
      Nomoto Munetaka、Konopaske Glenn T.、Yamashita Naoya、Hirayasu Yoshio、Snyder Evan Y.、Goshima Yoshio et al.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 31 Pages: 1-7

    • DOI

      10.1073/pnas.2100032118

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NGF Signaling in Endosomes2021

    • Author(s)
      Yamashita N
    • Journal Title

      Advances in Experimental Medicine and Biology

      Volume: 1331 Pages: 19-29

    • DOI

      10.1007/978-3-030-74046-7_3

    • ISBN
      9783030740450, 9783030740467
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activity‐induced secretion of semaphorin 3A mediates learning2021

    • Author(s)
      Jitsuki‐Takahashi Aoi、Jitsuki Susumu、Yamashita Naoya、Kawamura Meiko、Abe Manabu、Sakimura Kenji、Sano Akane、Nakamura Fumio、Goshima Yoshio、Takahashi Takuya
    • Journal Title

      European Journal of Neuroscience

      Volume: 00 Issue: 10 Pages: 1-15

    • DOI

      10.1111/ejn.15210

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphorylation of CRMP2 is required for migration and positioning of Purkinje cells: Redundant roles of CRMP1 and CRMP42020

    • Author(s)
      Yamazaki Yuki、Nagai Jun、Akinaga Satoshi、Koga Yumeno、Hasegawa Masaya、Takahashi Miyuki、Yamashita Naoya、Kolattukudy Papachan、Goshima Yoshio、Ohshima Toshio
    • Journal Title

      Brain Research

      Volume: 1736 Pages: 146762-146762

    • DOI

      10.1016/j.brainres.2020.146762

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Axonal targeting of TrkA-APP complex via transcytosis2023

    • Author(s)
      Naoya Yamashita
    • Organizer
      Neurotrophic Mechanisms in Health and Disease Gordon Research Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of APP-PlexinA interaction in NGF-dependent APP metabolism2023

    • Author(s)
      Takumi Sekiguchi, Takashi Sakurai, Naoya Yamashita
    • Organizer
      Neurotrophic Mechanisms in Health and Disease Gordon Research Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Aβ産生制御におけるAPP-PlexinAシグナルの機能解析2023

    • Author(s)
      関口 拓己、櫻井 隆、山下 直也
    • Organizer
      第148回日本薬理学会関東部会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 成体脳におけるセマフォリン3A発現を定量するELISAシステムの確立2023

    • Author(s)
      杉山 黎、林 克儀、中村 史雄、櫻井 隆、五嶋 良郎、山下 直也
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 成体脳におけるセマフォリン3A発現を定量するELISAシステムの確立.2022

    • Author(s)
      古川 涼音, 小林 瑞季, 林 克儀, 中村 史雄, 櫻井 隆, 五嶋 良郎, 山下 直也
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Semaphorin3A-PlexinAシグナルがアミロイドβ前駆タンパク質の機能や代謝に与える影響.2022

    • Author(s)
      関口 拓己, 櫻井 隆, 山下 直也
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] 成体脳におけるセマフォリン3A発現を定量するELISAシステムの確立2022

    • Author(s)
      山下 直也、水谷 由衣、實木-高橋 葵、林 克儀、中村 史雄、櫻井 隆 、五嶋 良郎
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Axonal targeting of TrkA-APP complex via transcytosis2021

    • Author(s)
      山下直也、櫻井隆
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Axonal targeting of TrkA-APP complex via transcytosis2021

    • Author(s)
      Yamashita Naoya、Sakurai Takashi
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Axonal targeting of TrkA signaling complex via transcytosis2020

    • Author(s)
      Yamashita Naoya、Sakurai Takashi
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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