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Tauopathy Analysis of tau phosphorylation specific to neurodegenerative diseases and elucidation of pathogenic factors

Research Project

Project/Area Number 17K07113
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTokyo Metropolitan Institute of Medical Science (2019-2020)
National Institutes for Quantum and Radiological Science and Technology (2017-2018)

Principal Investigator

KIMURA Taeko  公益財団法人東京都医学総合研究所, 脳・神経科学研究分野, 研究員 (60748820)

Co-Investigator(Kenkyū-buntansha) 久永 眞市  東京都立大学, 理学研究科, 客員教授 (20181092)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsタウ / リン酸化 / Phos-Tag SDS-PAGE / マーモセット / タウオパチー / アルツハイマー病 / Phos-Tag / 嗜銀顆粒性認知症 / 皮質基底核変性症 / ピック病 / phosphorylation / タウアイソフォーム / Cdk / 核局在 / Thr231 / Tau / リン酸化解析 / イメージング
Outline of Final Research Achievements

Tauopathy is a group of neurodegenerative diseases, including Alzheimer's disease (AD), characterized by aggregates containing abnormally phosphorylated tau. The role of tau site-specific phosphorylation has not been clarified physiologically or pathologically. In this study, we used the Phos-tag method, which can quantitatively and combine phosphorylation, to perform a detailed analysis of tau phosphorylation in marmosets, which are primates similar to humans and are highly useful as pathological models. This may be applicable to applied research in non-human primates. In addition, the phosphorylation of aggregated tau in patients with multiple tauopathy neurodegenerative diseases was analyzed in detail, and the phosphor specific tau isotype to each tauopathy was clarified.

Academic Significance and Societal Importance of the Research Achievements

現在日本では高齢化が急速に進み、2025年には認知症患者数が700万人を超えると予測されている。そのため認 知症の予防、診断、治療の開発が急務な課題となっている。アルツハイマー病(AD)など神経変性疾患では、発病 原因に関わる病理変化は死後脳における確定診断として用いられているが、それらの臨床診断への応用は確立していなかった。本研究は、各タウオパチー神経変性疾患における凝集性タウのリン酸 化状態を詳しく解析し、各タウオパチー特異的なリン酸化アイソタイプを同定する。そしてその形成メカニズムを探索し、リン酸化の制御を標的とした各タウオパチー特異的な治療開発に近づけるのではないかと考えている。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (15 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Tau isoform expression and phosphorylateion in marmotset brains.2019

    • Author(s)
      Sharma G, Huo A, Kimura T, Shiozawa S, Kobayashi R, Sahara N, Ishibashi M, Ishigaki S, Saito T, Ando K, Murayama S, Hasegawa M, Sobue G, Okano H, Hisanaga SI.
    • Journal Title

      J Biol Chem.

      Volume: 26;294(30) Pages: 11433-11444

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pathological progression induced by the frontotemporal dementia-associated R406W tau mutation in patient-derived iPSCs.2019

    • Author(s)
      Nakamura M, Shiozawa S, Tsuboi D, Amano M, Watanabe H, Maeda S, Kimura T, Yoshimatsu S, Kisa F, Karch CM, Miyasaka T, Takashima A, Sahara N, Hisanaga S, Ikeuchi T, Kaibuchi K, Okano H
    • Journal Title

      Stem Cell Reports.

      Volume: 8;13(4) Pages: 684-699

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biochemical Properties of Pathology-Related Tau Species in Tauopathy Brains: An Extraction Protocol for Tau Oligomers and Aggregates2018

    • Author(s)
      Sahara Naruhiko、Kimura Taeko
    • Journal Title

      Methods Mol Biol

      Volume: 1007 Pages: 435-445

    • DOI

      10.1007/978-1-4939-7816-8_26

    • ISBN
      9781493978151, 9781493978168
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tau Fibril Formation in Cultured Cells Compatible with a Mouse Model of Tauopathy2018

    • Author(s)
      Matsumoto Gen、Matsumoto Kazuki、Kimura Taeko、Suhara Tetsuya、Higuchi Makoto、Sahara Naruhiko、Mori Nozomu
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 5 Pages: 1497-1497

    • DOI

      10.3390/ijms19051497

    • NAID

      120006988072

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isoform-independent and -dependent phosphorylation of microtubule-associated protein tau in mouse brain during postnatal development.2018

    • Author(s)
      Tuerde, D., Kimura, T., Miyasaka, T., Furusawa, K., Shimozawa, A., Hasegawa, M., Ando, A., Hisanaga, S.
    • Journal Title

      J. Biol, Chem.

      Volume: 293 Issue: 5 Pages: 1781-1793

    • DOI

      10.1074/jbc.m117.798918

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phospho-Tau Bar Code: Analysis of Phosphoisotypes of Tau and Its Application to Tauopathy2018

    • Author(s)
      Kimura T, Sharma G, Ishiguro K, Hisanaga SI
    • Journal Title

      Front Neurosci

      Volume: 12 Pages: 44-44

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo regulation of glycogen synthase kinase 3β activity in neurons and brains.2017

    • Author(s)
      Krishnankutty, A., Kimura, T., Saito, T., Aoyagi, K., Asada, A., Takahashi, S., Ando, K., Ohara-Imaizumi, M., Ishiguro, K., Hisanaga, S.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 8602-8602

    • DOI

      10.1038/s41598-017-09239-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phos-tag SDS-PAGE analysis of complicated phosphorylation of a neurodegenerative disease protein tau2017

    • Author(s)
      木村 妙子、久永 眞市
    • Journal Title

      Electrophoresis Letters

      Volume: 61 Issue: 2 Pages: 49-52

    • DOI

      10.2198/electroph.61.49

    • NAID

      130006207357

    • ISSN
      2189-2628, 2189-2636
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] [18F]PM-PBB3 PET imaging of Tau deposition in the tauopathy model mice. poster presentation.2019

    • Author(s)
      Taeko Kimura, Chie Seki, Kazuaki Sampei, Jun Maeda, Maiko Ono, Tetsuya Suhara, Ming-Rong Zhang, Naruhiko Sahara and Makoto Higuchi
    • Organizer
      The 29th international symposium on cerebral blood flow, metabolism and function. The 14th international conference on quantification of Brain function with PET.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Phospho-Tau Bar Code: Analysis of Phosphoisotypes of Tau and Its Application to Tauopathy.2018

    • Author(s)
      木村妙子
    • Organizer
      第40回日本生物学的精神医学会 第61回日本神経化学会大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] タウモデルマウスを用いた新規タウPETリガンド[18F]PM-PBB3の有用性2018

    • Author(s)
      木村妙子
    • Organizer
      新学術領域研究 脳タンパク質老化と認知症制御 第8回班員会議・第4回リトリート
    • Related Report
      2018 Research-status Report
  • [Presentation] タウモデルマウスを用いた新規タウPETリガンド[18F]PM-PBB3の有用性2018

    • Author(s)
      木村妙子
    • Organizer
      第37回日本認知症学会学
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of in vivo imaging platform for investigating pathological tau propagation2017

    • Author(s)
      木村妙子
    • Organizer
      新学術領域研究「脳タンパク質老化と認知症制御」第2回国際シンポジウム
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 複雑怪奇なリン酸化タンパク質タウのPhos-Tag解析2017

    • Author(s)
      木村妙子,久永眞市
    • Organizer
      第68回日本電気泳動学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] タウオパチー神経変性疾患と脳内炎症2020

    • Author(s)
      木村妙子, 久永眞市, 長谷川成人
    • Total Pages
      5
    • Publisher
      別冊BIO Clinica
    • Related Report
      2020 Annual Research Report

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Published: 2017-04-28   Modified: 2023-03-16  

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