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The analysis of clearance mechanism of oxygenated Abeta

Research Project

Project/Area Number 18K06653
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionThe University of Tokyo

Principal Investigator

Hori Yukiko  東京大学, 大学院薬学系研究科(薬学部), 講師 (80610683)

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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords神経変性疾患 / 神経科学 / 脳神経疾患
Outline of Final Research Achievements

Alzheimer disease is caused by the accumulation of amyloid, called as amyloid β peptide (Aβ) and tau, in the brain. We previously developed an artificial photo-oxygenation system using a low molecular weight catalytic compound, photocatalyst. And we also have revealed the possibility that this amyloid selective photo-oxygenation inhibited the aggregation and facilitated the clearance of already formed amyloid. However, the mechanism of facilitated clearance by photo-oxygenation was unclear.
In this study, we found that the structural and biochemical properties of amyloid were changed by photo-oxygenation. We also revealed that microglia were responsible cells in brain for facilitated degradation of photo-oxygenated Aβ, and that lysosomal degrading enzymes within these cells were involved in degradation. These results suggest that photo-oxygenation have possibility as a novel therapeutic strategy against Alzheimer disease.

Academic Significance and Societal Importance of the Research Achievements

高齢者認知症の多くを占めるADは、大きな社会問題となっている。脳内でのアミロイドの蓄積がAD発症の原因であることから、アミロイド形成を抑制し、既に蓄積したアミロイドを効率よく除去することがAD根本治療戦略として考えられているが、未だ根本治療法確立には至っていない。本研究成果は、凝集Aβやタウに対する光酸素化法の新規AD根本治療戦略としての可能性を示した点で意義がある。また光酸素化触媒はアミロイドに共通の立体構造に対して反応し活性化することから、パーキンソン病や筋萎縮性側索硬化症などの、AD以外のアミロイド形成・蓄積を原因とする多くの神経変性疾患に対しても有用である可能性が期待される。

Report

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

    (21 results)

All 2021 2020 2019 2018 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results) Remarks (2 results)

  • [Journal Article] Photo-oxygenation by a biocompatible catalyst reduces amyloid-β levels in the brains of Alzheimer’s disease model mice2021

    • Author(s)
      Ozawa S, Hori Y, Shimizu Y, Taniguchi A, Suzuki T, Wang W, Chiu YW, Koike R, Yokoshima S, Fukuyama T, Takatori S, Sohma Y, Kanai M, Tomita T
    • Journal Title

      Brain

      Volume: - Issue: 6 Pages: 1884-1897

    • DOI

      10.1093/brain/awab058

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Catalytic photooxygenation degrades brain Aβ in vivo2021

    • Author(s)
      Nagashima Nozomu、Ozawa Shuta、Furuta Masahiro、Oi Miku、Hori Yukiko、Tomita Taisuke、Sohma Youhei、Kanai Motomu
    • Journal Title

      Science Advances

      Volume: 7 Issue: 13 Pages: 0-1

    • DOI

      10.1126/sciadv.abc9750

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Photo-oxygenation: an innovative new therapeutic approach against amyloidoses2021

    • Author(s)
      Ikeda T, Hori Y, Sohma Y, Kanai M, and Tomita T
    • Journal Title

      Adv Exp Med Biol.

      Volume: -

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] EphA4 regulates Aβ production via BACE1 expression in neurons2020

    • Author(s)
      Tamura Kensuke、Chiu Yung‐Wen、Shiohara Azusa、Hori Yukiko、Tomita Taisuke
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 12 Pages: 16383-16396

    • DOI

      10.1096/fj.202001510r

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Photo-oxygenation inhibits tau amyloid formation2019

    • Author(s)
      Suzuki T*, Hori Y*, Sawazaki T, Shimizu Y, Nemoto Y, Taniguchi A, Ozawa S, Sohma Y, Kanai M, Tomita T
    • Journal Title

      Chem. Commun.

      Volume: 55(44) Issue: 44 Pages: 6165-6168

    • DOI

      10.1039/c9cc01728c

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD2-associated protein (CD2AP) overexpression accelerates amyloid precursor protein (APP) transfer from early endosomes to the lysosomal degradation pathway2019

    • Author(s)
      Furusawa K, Takasugi T, Chiu YW, Hori Y, Tomita T, Fukuda M, Hisanaga SI
    • Journal Title

      J. Biol. Chem.

      Volume: 294(28) Issue: 28 Pages: 10886-10899

    • DOI

      10.1074/jbc.ra118.005385

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Retrograde transport of γ-secretase from endosomes to the trans-Golgi network regulates Aβ42 production.2018

    • Author(s)
      Kanatsu K, Hori Y, Ebinuma I, Chiu YW, Tomita T
    • Journal Title

      J. Neurochem.

      Volume: 147(1) Issue: 1 Pages: 110-123

    • DOI

      10.1111/jnc.14477

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 新規光酸素化触媒による非侵襲的光酸素化反応の確立2020

    • Author(s)
      堀由起子、永島臨、小澤柊太、相馬洋平、金井求、富田泰輔
    • Organizer
      第39回日本認知症学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マイクログリアによる光酸素化Aβ代謝促進機構の解明2020

    • Author(s)
      小澤柊太、谷口敦彦、清水裕介、王文博、小池礼子、横島聡、福山透、高鳥翔、相馬洋平、金井求、堀由起子、富田泰輔
    • Organizer
      第39回日本認知症学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] APP依存的な新規タウ分泌現象の発見2020

    • Author(s)
      佐藤玄謙、堀由起子、春日健作、池内健、富田泰輔
    • Organizer
      第39回日本認知症学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 光酸素化触媒を用いた新規AD治療戦略の開発2020

    • Author(s)
      堀由起子
    • Organizer
      第24回 Neurology SPECT定量検討会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Development of photooxygenation technology towards therapeutic strategy against Alzheimer disease2020

    • Author(s)
      Yukiko Hori
    • Organizer
      UTokyo-Cambridge Voices Workshop on the future of therapeutic development against neurodegenerative diseases
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Photooxygenation inhibits tau amyloid formation2019

    • Author(s)
      Hori Y, Suzuki T, Sawazaki T, Shimizu Y, Nemoto Y, Taniguchi A, Ozawa S, Sohma Y, Kanai M, Tomita T
    • Organizer
      Society for Neuroscience 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The effect of synaptic adhesion molecules on in vitro tau propagation model2019

    • Author(s)
      Nemoto Y, Hori Y, Tomita T
    • Organizer
      Society for Neuroscience 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 光酸素化反応による酸素化Aβの代謝機構の解析2019

    • Author(s)
      堀由起子、小澤柊太、清水裕介、谷口敦彦、相馬洋平、金井求、富田泰輔
    • Organizer
      日本認知症学会
    • Related Report
      2019 Research-status Report
  • [Presentation] アルツハイマー病治療を目指した光酸素化触媒によるタウアミロイド動態制御2019

    • Author(s)
      鈴木崇允、堀由起子、澤崎鷹、清水裕介、根本侑、谷口敦彦、小澤柊太、相馬洋平、金井求、富田泰輔
    • Organizer
      日本認知症学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Photooxygenation reduces the Ab level in the brains of Alzheimer disease model mice2019

    • Author(s)
      Yukiko Hori
    • Organizer
      第9回アジア・オセアニア生理学会連合大会(9th FAOPS2019)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Photooxygenation by biocompatible catalyst reduces the Aβ level in the brains of Alzheimer disease model mice.2018

    • Author(s)
      Shuta Ozawa, Yukiko Hori, Takanobu Suzuki, Youhei Sohma, Motomu Kanai, Taisuke Tomita
    • Organizer
      Society for Neuroscience 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 光酸素化触媒によるタウの酸素化は凝集を抑制する2018

    • Author(s)
      鈴木崇允、堀由起子、澤崎鷹、根本侑、小澤柊太、相馬洋平、金井求、富田泰輔
    • Organizer
      2018年度生化学会関東支部例会
    • Related Report
      2018 Research-status Report
  • [Remarks] 東京大学薬学系研究科 機能病態学教室 ホームページ

    • URL

      http://www.f.u-tokyo.ac.jp/~neuropsc/tomita/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 東京大学大学院薬学系研究科 機能病態学教室

    • URL

      http://www.f.u-tokyo.ac.jp/~neuropsc/tomita/index.html

    • Related 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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