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Research on the regulatory mechanism of synaptic amyloid beta production by SV2B

Research Project

Project/Area Number 18K15365
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionKyoto University

Principal Investigator

Miyamoto Masakazu  京都大学, 医学研究科, 特定助教 (80816736)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsアルツハイマー病 / βセクレターぜ / シナプス / シナプス小胞タンパク2B / Aβ / synapse / BACE1 / SV2B / βセクレターゼ / アミロイドβ / SV2A
Outline of Final Research Achievements

Aβ oligomers at synapses have been reported to be associated with the development of dementia, and controlling the cleavage of APP by BACE1 at synapses could be a new AD treatment strategy. We identified synaptic vesicle protein 2B (SV2B) as a regulator of BACE1 at synapses and found that SV2B is involved in the localization of BACE1 at synapses. As a result of searching for proteins involved in the interaction of SV2B / BACE1, Tubulin alpha 1C, Myelin proteolipid protein, and 60 kDa Heat shock protein were identified as candidate proteins.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病は認知症の大部分を占め、その制圧と対応は世界的に、特に我が国のような高齢化に直面し認知症患者が増加している国々においては特に喫緊の問題となっている。アルツハイマー型認知症の根本的治療としてアミロイドβ蛋白(Aβ)抗体療法が近年期待されているが、多額のコストの問題などを孕んでおり、その他の治療方法の開発は今後も重要であり続けるものと考えられる。シナプスにおけるBACE1によるAPP切断を生理的に制御する分子機序の解明はシナプスを標的とした新規モジュレーター型BACE1阻害剤の開発研究の礎になることが期待され、本研究の成果がその一助となるものと考えられる。

Report

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

    (5 results)

All 2021 2020 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (4 results)

  • [Journal Article] Synaptic Vesicle Protein 2B Negatively Regulates the Amyloidogenic Processing of AβPP as a Novel Interaction Partner of BACE12020

    • Author(s)
      Miyamoto Masakazu、Kuzuya Akira、Noda Yasuha、Ueda Sakiho、Asada-Utsugi Megumi、Ito Shinji、Fukusumi Yoshiyasu、Kawachi Hiroshi、Takahashi Ryosuke、Kinoshita Ayae
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: Apr 6 Issue: 1 Pages: 1-13

    • DOI

      10.3233/jad-200071

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] A search for novel synaptic proteins associated with BACE1/SV2B interaction2021

    • Author(s)
      Masakazu Miyamoto, Akira Kuzuya, Sakiho Ueda, Mizuki Matsumoto, Shinji Ito, Yoshiyasu Fukusumi, Hiroshi Kawachi, Ryousuke Takahashi
    • Organizer
      第62回日本神経学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Synaptic vesicle protein 2B is a novel interaction partner of BACE12020

    • Author(s)
      Masakazu Miyamoto, Akira Kuzuya, Yasuha Noda, Kengo Uemura, Megumi Asada-Utsugi, Shinji Ito, Yoshiyasu Fukusumi, Hiroshi Kawachi, Ryousuke Takahashi, Ayae Kinoshita
    • Organizer
      第39回日本認知症学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] SV2B can regulate BACE1 localization2018

    • Author(s)
      Masakazu Miyamoto
    • Organizer
      第59回神経学会
    • Related Report
      2018 Research-status Report
  • [Presentation] SV2B can regulate BACE1 localization and its activity2018

    • Author(s)
      Masakazu Miyamoto
    • Organizer
      第41回神経科学会
    • Related Report
      2018 Research-status Report

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

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