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Development of a novel neurovascular treatment for tauopathy

Research Project

Project/Area Number 17K14958
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Satoshi Saito  国立研究開発法人国立循環器病研究センター, 病院, 医師 (40732996)

Research Collaborator Ihara Masafumi  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsアルツハイマー病 / 脳アミロイド血管症 / シロスタゾール / タキシフォリン / β-amyloid / tau / cilostazol / taxifolin / タウ / 脳血管病変 / 痴呆 / 神経科学 / トランスレーショナルリサーチ
Outline of Final Research Achievements

Resent investigations have revealed that the cerebral blood flow and the clearance of interstitial fluid from the neuron is much dependent on the state of cerebral microcirculation, suggesting that the maintenance of cerebrovascular integrity is important not only for prevention of cerebrovascular disease but also for amelioration of neurodegenerative diseases including Alzheimer’s disease (AD). Pathological hallmarks of AD are senile plaque, cerebral amyloid angiopathy (CAA), and neurofibrillary tangle. The former two changes are based on amyloidosis and the latter is tauopathy. CAA is observed in more than 80% of AD cases. CAA impairs cerebrovascular reactivity and causes both hemorrhagic and ischemic strokes, attributing to cognitive impairment. Most CAA is a consequence of Aβ elimination failure, mainly caused by disturbance of intramural periarterial drainage (IPAD) or glymphatic system. Therefore, facilitation of Aβ clearance would be a potential treatment for dementia.

Academic Significance and Societal Importance of the Research Achievements

認知症は高齢社会における最大の課題の一つである. 本研究はcilostazolとtaxifolinの併用療法の有用性を示し, 認知症治療における新たな治療薬の可能性を見出した点が, 社会的に重要である.

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] University of Southampton/University of Newcastle(英国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy2019

    • Author(s)
      Inoue Takayuki、Saito Satoshi、Tanaka Masashi、Yamakage Hajime、Kusakabe Toru、Shimatsu Akira、Ihara Masafumi、Satoh-Asahara Noriko
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel therapeutic potentials of taxifolin for amyloid-beta associated neurodegenerative diseases and other diseases: recent advances and future perspectives2019

    • Author(s)
      Tanaka Masashi、Saito Satoshi、Inoue Takayuki、Satoh-Asahara Noriko、Ihara Masafumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a multicomponent intervention to prevent Alzheimer’s disease2019

    • Author(s)
      Saito Satoshi、Yamamoto Yumi、Ihara Masafumi
    • Journal Title

      Frontiers in Neurology

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 脳アミロイド血管症の新規治療薬の開発2018

    • Author(s)
      齊藤聡
    • Journal Title

      脳循環代謝

      Volume: 印刷中

    • NAID

      130007437991

    • Related Report
      2017 Research-status Report
  • [Journal Article] Taxifolin inhibits amyloid-β oligomer formation and fully restores vascular integrity and memory in cerebral amyloid angiopathy2017

    • Author(s)
      Satoshi Saito, Yumi Yamamoto, Takakuni Maki, Yorito Hattori, Hideki Ito, Katsuhiko Mizuno, Mariko Harada-Shiba, Raj N. Kalaria, Masanori Fukushima, Ryosuke Takahashi, Masafumi Ihara
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 5 Issue: 1 Pages: 26-26

    • DOI

      10.1186/s40478-017-0429-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 脳微小循環とアミロイド、そしてタウ2019

    • Author(s)
      齊藤聡
    • Organizer
      第44回日本微小循環学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Novel Ci-Tax treatment reversed impaired cerebrovascular integrity and memory in cerebral amyloid angiopathy.2018

    • Author(s)
      齊藤聡
    • Organizer
      第61回日本脳循環代謝学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 認知症と脳血管障害とCnm陽性S.mutans2018

    • Author(s)
      齊藤聡
    • Organizer
      第37回日本認知症学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Novel Ci-Tax treatment reversed impaired cerebrovascular integrity and memory in cerebral amyloid angiopathy.2018

    • Author(s)
      Saito Satoshi
    • Organizer
      6th international CAA conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血液脳関門の破綻を食い止めるには ―脳アミロイド血管症の新規治療薬の開発―2017

    • Author(s)
      齊藤聡
    • Organizer
      第60回日本脳循環代謝学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 慢性脳低灌流はタウ病理を加速させる: 脳アミロイド血管症とタウとの関連2017

    • Author(s)
      齊藤聡、他
    • Organizer
      第60回日本脳循環代謝学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Taxifolin inhibits amyloid-β oligomer formation and fully restores vascular integrity and memory in cerebral amyloid angiopathy.2017

    • Author(s)
      Saito S, Yamamoto Y, Maki T, Fukushima M, Takahashi R, Ihara M.
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] リナグリプチンは糖尿病合併tauopathyマウスの脳血流量を回復し認知機能を改善させた2017

    • Author(s)
      中奥由里子、齊藤聡、他
    • Organizer
      第60回日本脳循環代謝学会学術集会
    • Related Report
      2017 Research-status Report
  • [Book] 『アルツハイマー病 発症メカニズムと新規診断法・創薬・治療開発』(分担「脳の”リンパ”機能を促進する新規アルツハイマー病治療薬の可能性」および表紙画像提供)2018

    • Author(s)
      齊藤聡
    • Total Pages
      6
    • Publisher
      エヌ・ティー・エス
    • Related Report
      2018 Annual Research Report
  • [Remarks] 国循で認知症予防!?

    • URL

      http://www.ncvc.go.jp/about/excellence/11.html

    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 認知症の予防及び/又は治療のための薬剤2017

    • Inventor(s)
      齊藤聡 他
    • Industrial Property Rights Holder
      齊藤聡 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report
    • Overseas

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Published: 2017-04-28   Modified: 2020-03-30  

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