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Development of novel therapeutic agents for schizophrenia based on kynurenine hypothesis

Research Project

Project/Area Number 17K01969
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical biology
Research InstitutionFujita Health University

Principal Investigator

Fujigaki Hidetsugu  藤田医科大学, 保健学研究科, 講師 (00612631)

Co-Investigator(Kenkyū-buntansha) 毛利 彰宏  藤田医科大学, 保健学研究科, 准教授 (20597851)
服部 恭尚  京都薬科大学, 薬学部, 講師 (20567028)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords統合失調症 / キヌレン酸 / トリプトファン代謝 / キヌレニンアミノトランスフェラーゼ
Outline of Final Research Achievements

Kynurenine aminotransferase 2 (KAT2) is an enzyme that catabolizes kynurenine to kynurenic acid (KYNA). Since the accumulation of KYNA in the brain has been reported to be involved in the pathology of schizophrenia, the regulation of KYNA production in the brain by KAT2 inhibitor may be useful for the treatment of schizophrenia. This study revealed that glycyrrhizic acid (GL) and its derivatives are KAT2 inhibitors. These compounds may be useful as therapeutic agents for schizophrenia.

Academic Significance and Societal Importance of the Research Achievements

本研究により、グリチルリチン酸やその誘導体はKAT2阻害剤であることが明らかになったことから、これらの化合物は統合失調症の治療薬として利用できる可能性がある。また、これらの化合物は甘草の根に含まれる成分であり、医薬品や漢方薬の有効成分として広く用いられている。グリチルリチン酸を含む漢方薬には統合失調症の症状を緩和させるという報告もあり、グリチルリチン酸の作用の一つとしてKAT2阻害が関与することが示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Selective and competitive inhibition of kynurenine aminotransferase 2 by glycyrrhizic acid and its analogues2019

    • Author(s)
      Yoshida Yukihiro、Fujigaki Hidetsugu、Kato Koichi、Yamazaki Kyoka、Fujigaki Suwako、Kunisawa Kazuo、Yamamoto Yasuko、Mouri Akihiro、Oda Akifumi、Nabeshima Toshitaka、Saito Kuniaki
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 10243-10243

    • DOI

      10.1038/s41598-019-46666-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Indoleamine 2,3‐dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma2019

    • Author(s)
      Yamasuge Wakana、Yamamoto Yasuko、Fujigaki Hidetsugu、Hoshi Masato、Nakamoto Kentaro、Kunisawa Kazuo、Mouri Akihiro、Nabeshima Toshitaka、Saito Kuniaki
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 10 Pages: 3061-3067

    • DOI

      10.1111/cas.14179

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Linking phencyclidine intoxication to the tryptophan-kynurenine pathway: Therapeutic implications for schizophrenia2019

    • Author(s)
      Fujigaki Hidetsugu、Mouri Akihiro、Yamamoto Yasuko、Nabeshima Toshitaka、Saito Kuniaki
    • Journal Title

      Neurochemistry International

      Volume: 125 Pages: 1-6

    • DOI

      10.1016/j.neuint.2019.02.001

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lipopolysaccharide shock reveals the immune function of indoleamine 2,3-dioxygenase 2 through the regulation of IL-6/stat3 signalling2018

    • Author(s)
      Yamamoto Yasuko、Yamasuge Wakana、Imai Shinjiro、Kunisawa Kazuo、Hoshi Masato、Fujigaki Hidetsugu、Mouri Akihiro、Nabeshima Toshitaka、Saito Kuniaki
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 15917-15917

    • DOI

      10.1038/s41598-018-34166-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Tryptophan metabolites as a potential tumor marker2019

    • Author(s)
      Fujigaki Hidetsugu
    • Organizer
      15th Asia-Pacific Federation for Clinical Biochemistry and Laboratory Medicine Congress.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 液体クロマトグラフ質量分析計(LC-MS)によるトリプトファン代謝産物一斉定量解析2019

    • Author(s)
      木村 文香, 村上 怜子, 藤垣 英嗣, 國澤 和生, 毛利 彰宏, 仲本 賢太郎, 山本 康子, 鍋島 俊隆, 齋藤 邦明
    • Organizer
      第59回日本臨床化学会年次学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] グリチルリチン酸とその類似体はキヌレニンアミノトランスフェラーゼ2活性を阻害する2019

    • Author(s)
      藤垣英嗣,吉田幸弘,加藤紘一,小田彰史,山本康子,鍋島俊隆,齋藤邦明
    • Organizer
      第39回日本トリプトファン研究会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development and Validation of a Liquid Chromatography Tandem Mass Spectrometry Method for the Measurement of Tryptophan Metabolites2019

    • Author(s)
      Hidetsugu Fujigaki, Reiko Murakami, Yasuko Yamamoto, Kuniaki Saito
    • Organizer
      The 57th Congress of the Korean Association of Medical Technoligists and International Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] トリプトファン・キヌレニン代謝経路の変動と精神神経疾患2018

    • Author(s)
      藤垣 英嗣
    • Organizer
      第58回日本臨床化学会年次学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Kynurenine 3-monooxygenase is essential for de novo biosynthesis of NAD2018

    • Author(s)
      Yukihiro Yoshida, Hidetsugu Fujigaki, Yasuko Yamamoto, Kyoka Yamazaki, Tsutomu Fukuwatari, Toshitaka Nabeshima, Kuniaki Saito
    • Organizer
      15th International Society for Tryptophan Research Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of Kynurenine aminotransferase II inhibitor screening assay2018

    • Author(s)
      Kyoka Yamazaki, Hidetsugu Fujigaki, Yukihiro Yoshida, Yasuko Yamamoto, Toshitaka Nabeshima, Kuniaki Saito
    • Organizer
      15th International Society for Tryptophan Research Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterization and n-glycosylation detection of human kynurenine 3-monooxygenase2018

    • Author(s)
      Fumika Kimura, Hidetsugu Fujigaki, Yukihiro Yoshida, Yasuko Yamamoto, Toshitaka Nabeshima, Kuniaki Saito
    • Organizer
      15th International Society for Tryptophan Research Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Kynurenine 3-monooxygenase遺伝子R452C変異解析の基礎的検討2017

    • Author(s)
      藤垣英嗣、吉田幸弘、山本康子、齋藤邦明
    • Organizer
      第57回日本臨床化学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 酵素法を用いたキヌレニン定量法の開発2017

    • Author(s)
      吉田幸弘、藤垣英嗣、山本康子、齋藤邦明
    • Organizer
      第57回日本臨床化学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Kynurenine aminotransferase 2を用いたキヌレニン測定法の開発2017

    • Author(s)
      吉田幸弘、藤垣英嗣、山﨑杏佳、山本康子、齋藤邦明
    • Organizer
      第38回日本トリプトファン研究会学術集会
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] キヌレニンアミノトランスフェラーゼ2(KAT2)阻害剤2019

    • Inventor(s)
      藤垣 英嗣, 齋藤 邦明
    • Industrial Property Rights Holder
      藤垣 英嗣, 齋藤 邦明
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-061581
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] キヌレニンアミノトランスフェラーゼ2(KAT2)阻害剤2019

    • Inventor(s)
      藤垣英嗣、齋藤邦明
    • Industrial Property Rights Holder
      学校法人藤田学園
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-061581
    • Filing Date
      2019
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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