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Behavioral study on the novel anti-dementia drug repurposed as treatment for the Alzheimer's disease

Research Project

Project/Area Number 18K07460
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionTokyo Metropolitan Geriatric Hospital and Institute of Gerontology

Principal Investigator

Yanai Shuichi  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (60469070)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsアルツハイマー病 / 記憶・学習 / ドラッグ・リポジショニング / シロスタゾール / ドネペジル / 記憶 / 学習 / アルツハイマー型認知症 / 老化 / 2剤併用療法
Outline of Final Research Achievements

In the present study, we revealed that the PDE3 inhibitor cilostazol improved the impaired learning and memory function in a mouse model of Alzheimer’s disease. This results suggest that cilostazol might be a possible therapeutic intervention for the treatment of Alzheimer’s disease. In addition, sub-effective doses of cilostazol and donepezil in combination recovered memory function. These results suggest that the combination therapy comprising two or more drugs may offer a new pharmacological approach for treating cognitive disorders, as the combination therapy demonstrated to be an effective strategy for treating some types of diseases.

Academic Significance and Societal Importance of the Research Achievements

既存薬剤の主標的分子や作用機序を新規疾患へ展開するドラッグ・リポジショニングに立脚した国内外の研究の多くは、培養細胞等を用いた「分子・細胞レベル」の研究である。動物の「行動レベル」で認知症を対象としたドラッグ・リポジショニング研究は世界的に少ない。本研究で用いたシロスタゾールは既存薬と作用点が異なるため、アルツハイマー型認知症治療薬の選択肢を広げるとともに、既存の認知症治療薬との併用における有力な候補薬剤となることが期待される。認知機能低下を改善し、認知症の重篤症状を先送りすることは、個人の健康寿命ロスとQOLの低下を防ぐだけでなく、患者の家族を含む社会全体にとっての重要課題と言える。

Report

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

    (28 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (20 results) (of which Int'l Joint Research: 3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Tocotrienols reach the brain and play roles in the attenuation of body weight gain and improvement of cognitive function in high-fat diet-treated mice2021

    • Author(s)
      Yugo Kato, Hayami Uchiumi, Ryo Usami, Hirokatsu Takatsu, Yoshinori Aoki, Shuichi Yanai, Shogo Endo, Koji Fukui
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: -

    • NAID

      130008110247

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 認知症と老化に伴う記憶低下の予防と制御ー細胞内シグナル伝達系を標的としてー2020

    • Author(s)
      柳井修一・遠藤昌吾
    • Journal Title

      医学のあゆみ

      Volume: 273 Pages: 1095-1101

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vitamin C and vitamin E double-deficiency increased neuroinflammation and impaired conditioned fear memory2019

    • Author(s)
      Takahashi Keita、Yanai Shuichi、Takisawa Shoko、Kono Nozomu、Arai Hiroyuki、Nishida Yoichiro、Yokota Takanori、Endo Shogo、Ishigami Akihito
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 663 Pages: 120

    • DOI

      10.1016/j.abb.2019.01.003

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 8-Nitro-cGMP attenuates context-dependent fear memory in mice.2019

    • Author(s)
      Kishimoto Y, Kasamatsu S, Yanai S, Endo S, Akaike T, Ihara H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 511 Issue: 1 Pages: 141-147

    • DOI

      10.1016/j.bbrc.2019.01.138

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] PDE3 Inhibitors Repurposed as Treatments for Age-Related Cognitive Impairment2018

    • Author(s)
      Yanai Shuichi、Endo Shogo
    • Journal Title

      Molecular Neurobiology

      Volume: 印刷中 Issue: 6 Pages: 4306-4316

    • DOI

      10.1007/s12035-018-1374-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Kale supplementation up-regulates HSP70 and suppresses cognitive decline in a mouse model of accelerated senescence2018

    • Author(s)
      Kushimoto Shoko、Uchibori Yuki、Yanai Shuichi、Makabe Hidefumi、Nakamura Soichiro、Katayama Shigeru
    • Journal Title

      Journal of Functional Foods

      Volume: 44 Pages: 292-298

    • DOI

      10.1016/j.jff.2018.03.011

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 加齢に伴う皮質・運動機能低下に対するCoQ10投与の効果2020

    • Author(s)
      井上律子・柳井修一・三浦正巳
    • Organizer
      第17回日本コエンザイムQ協会研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ホスホジエステラーゼ3阻害剤シロスタゾールによる老化マウスの記憶機能低下の改善と予防2020

    • Author(s)
      柳井修一・新崎智子・遠藤昌吾
    • Organizer
      TOBIRA第9回研究交流フォーラム
    • Related Report
      2020 Annual Research Report
  • [Presentation] Amelioration of age-related spatial memory impairment by concurrent administration of sub-effective doses of donepezil and cilostazol2020

    • Author(s)
      Shuichi Yanai, Tomoko Arasaki, Shogo Endo
    • Organizer
      第43回日本基礎老化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Inhibitory effect of tocotrienols on weight gain in different mouse models2020

    • Author(s)
      Yugo Kato, Shogo Endo, Shuichi Yanai, Koji Fukui
    • Organizer
      第43回日本基礎老化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 転職する既存薬剤:抗血小板薬から記憶障害治療薬へのリポジショニング2020

    • Author(s)
      柳井修一
    • Organizer
      第62回日本老年医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Cilostazol, a phosphodiesterase 3 inhibitor, ameliorates spatial memory in APP knock-in mouse model of Alzheimer’s disease.2020

    • Author(s)
      Shuichi Yanai, Tomoko Arasaki, Takashi Saito, Takaomi Saido, & Shogo Endo
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] PDE3阻害剤シロスタゾール:抗血小板薬から認知症治療薬へのドラッグ・リポジショニング2020

    • Author(s)
      柳井修一・新崎智子・遠藤昌吾
    • Organizer
      日本心理学会第84回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 18F-標識ネオペンチルスチリルピリジンアミロイド-β PETプローブの生物学的評価2020

    • Author(s)
      多胡哲郎・豊原潤・ソウエイソウ・龍田真帆・新崎智子・柳井修一・遠藤昌吾・斉藤貴志・西道隆臣・田中浩士
    • Organizer
      第60回日本核医学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ICER過剰発現マウスの記憶に与えるシロスタゾールの効果2019

    • Author(s)
      高橋彩恵・柳井修一・福井浩二・遠藤昌吾
    • Organizer
      日本行動科学学会第35回ウィンターカンファレンス
    • Related Report
      2019 Research-status Report 2018 Research-status Report
  • [Presentation] PDE3阻害剤シロスタゾールによる血液脳関門・記憶機能の改善2019

    • Author(s)
      柳井修一・新崎智子・遠藤昌吾
    • Organizer
      TOBIRA第8回研究交流フォーラム
    • Related Report
      2019 Research-status Report
  • [Presentation] Concurrent administration of sub-effective doses of donepezil and phosphodiesterase 3 inhibitor cilostazol restores memory impairment in aged mice2019

    • Author(s)
      Shuichi Yanai, Tomoko Arasaki, & Shogo Endo
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 有酸素トレーニングが老齢マウス脳内のインスリン分解酵素のS-ニトロソ化に及ぼす影響2019

    • Author(s)
      張碩文・篠崎昇平・柳井修一・松本綾子・中本英子・小林裕幸・金木正夫・遠藤昌吾・後藤佐多良・内藤久士
    • Organizer
      第74回 日本体力医学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Amelioration of potentially harmful oxidative and nitrosative protein modifications by regular exercise in aged animals: A molecular mechanism of the beneficial effects2019

    • Author(s)
      Sataro Goto, Shuo-wen Chang, Shohei Shinozaki, Shuichi Yanai, Hideko Nakamoto, Ayako Matsumoto, Hisashi Naito, Hiroyuki Kobayshi, Masao Kaneki, Shogo Endo, & Zsolt Radak
    • Organizer
      11th International Association of Gerontology and Geriatrics Asia/Oceania Regional Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The effects of hearing loss and mobility decline on cognitive function of older adults2019

    • Author(s)
      Ryota Sakurai, Hisashi Kawai, Shuich Yanai, Hiroyuki Suzuki, Susumu Ogawa, Hunkyung Kim, Hirohiko Hirano, Kazushige Ihara, Shuichi Obuchi, Yoshinori Fujiwara
    • Organizer
      Gerontological Society of America 2019 Annual Scientific Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 老化促進モデルマウスSAMP8の記憶障害に対するシロスタゾールの効果2019

    • Author(s)
      柳井修一・新崎智子・遠藤昌吾
    • Organizer
      次世代脳プロジェクト 冬のシンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] 機能性食品による老化制御戦略2019

    • Author(s)
      柳井修一・池谷真澄
    • Organizer
      第42回日本基礎老化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Cilostazol, a phosphodiesterase 3 inhibitor, maintains and improves memory functions in aged mice.2018

    • Author(s)
      Shuichi Yanai, Tomoko Arasaki, & Shogo Endo
    • Organizer
      Neuroscience 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Recovery from spatial memory deficits and increase of cerebral glucose uptake in cilostazol-administered aged mice2018

    • Author(s)
      Shuichi Yanai, Tetsuro Tago, Jun Toyohara, Tomoko Arasaki, & Shogo Endo
    • Organizer
      第41回日本基礎老化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] The phosphodiesterase 3 inhibitor cilostazol restores memory impairment and enhances cerebral glucose metabolism in aged mice.2018

    • Author(s)
      Shuichi Yanai, Tetsuro Tago, Jun Toyohara, Tomoko Arasaki, & Shogo Endo
    • Organizer
      The phosphodiesterase 3 inhibitor cilostazol restores memory impairment and enhances cerebral glucose metabolism in aged mice.
    • Related Report
      2018 Research-status Report
  • [Presentation] 認知症との共生社会を支える基礎研究2018

    • Author(s)
      柳井修一・高瀬堅吉・山口哲生
    • Organizer
      日本心理学会第82回大会
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 加齢に伴う認知機能の低下予防又は改善用の組成物2020

    • Inventor(s)
      遠藤昌吾・柳井修一・飯田哲郎・新谷智也
    • Industrial Property Rights Holder
      遠藤昌吾・柳井修一・飯田哲郎・新谷智也
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 小動物用運動測定装置2019

    • Inventor(s)
      柳井修一・桜井良太・内田正幸
    • Industrial Property Rights Holder
      柳井修一・桜井良太・内田正幸
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report

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

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