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The expression analysis of Tau protein in hiPSC-derived neurons or directly converted neurons from fibroblasts

Research Project

Project/Area Number 17H07087
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionKeio University

Principal Investigator

Maeda Sumihiro  慶應義塾大学, 医学部(信濃町), 講師 (70443025)

Research Collaborator TAKASHIMA Akihiko  学習院大学, 理学部, 教授 (00154774)
Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsタウタンパク質 / 神経変性疾患 / 老化 / 脳 / アルツハイマー病 / FTDP-17 / 脳神経疾患
Outline of Final Research Achievements

Tau protein accumulation is a pathological hallmark observed in various neurodegenerative diseases including Alzheimer’s disease (AD). Tau accumulation at lesser extent is even observed in normal aging. Recent failures in the therapy development of AD based on mouse models implied the requirement of the pathomechanism validation using human cells for human diseases. Thus, we established neuronal cultures derived from human induced pluripotent stem cell or directly converted neurons from fibroblast to conserve the aging signature of the cells to model tau- and aging-dependent diseases including AD.

Academic Significance and Societal Importance of the Research Achievements

タウタンパク質の蓄積は、アルツハイマー病をはじめとする様々な神経変性疾患において観察されるのみならず、正常老化においても観察される現象であり、脳機能の年齢依存的な低下と深い関連性があるとされている。そのタウタンパク質の機能解析を、年齢依存的変化がキャンセルされたiPS細胞由来神経、および年齢依存的変化が保存されている体細胞から直接誘導された神経において行うことは、年齢とタウタンパク質の機能異常を解明する上で、非常に重要な系であった。今後、この系を用いて、タウタンパク質の機能異常を解明し、その治療薬を開発出来れば、超高齢社会を迎える日本においては、社会経済的にも非常に大きな意味がある。

Report

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

    (14 results)

All 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 8 results,  Invited: 5 results)

  • [Int'l Joint Research] The J. David Gladstone Institute(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Methylene Blue Inhibits Formation of Tau Fibrils but not of Granular Tau Oligomers: A Plausible Key to Understanding Failure of a Clinical Trial for Alzheimer’s Disease2019

    • Author(s)
      Soeda Yoshiyuki、Saito Marino、Maeda Sumihiro、Ishida Kohki、Nakamura Akira、Kojima Shuichi、Takashima Akihiko
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 68 Issue: 4 Pages: 1677-1686

    • DOI

      10.3233/jad-181001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frontotemporal dementia with Parkinsonism linked to chromosome-17 mutations enhance tau oligomer formation2018

    • Author(s)
      Maeda Sumihiro、Sato Yuhei、Takashima Akihiko
    • Journal Title

      Neurobiology of Aging

      Volume: 69 Pages: 26-32

    • DOI

      10.1016/j.neurobiolaging.2018.04.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuronal levels and sequence of tau modulate the power of brain rhythms2018

    • Author(s)
      Das Melanie、Maeda Sumihiro、Hu Bozhong、Yu Gui-Qiu、Guo Weikun、Lopez Isabel、Yu Xinxing、Tai Chao、Wang Xin、Mucke Lennart
    • Journal Title

      Neurobiology of Disease

      Volume: 117 Pages: 181-188

    • DOI

      10.1016/j.nbd.2018.05.020

    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] タウタンパク質研究における新たな潮流2018

    • Author(s)
      前田純宏
    • Journal Title

      オベリスク

      Volume: 23 Pages: 9-13

    • Related Report
      2017 Annual Research Report
  • [Presentation] Aggregation dependent and independent pathogenesis of Tau protein2018

    • Author(s)
      Sumihiro Maeda
    • Organizer
      Invited seminar at German Center for Neurodegenerative Disease
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuronal Levels and Sequence of Tau Modulate the Power of Brain Rhythms2018

    • Author(s)
      Sumihiro Maeda
    • Organizer
      Tau meeting 2018 at Kyoto
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Methylene blue inhibits formation of tau fibrils but not granular tau oligomers2018

    • Author(s)
      M. SAITO, Y. SOEDA, S. MAEDA, A. TAKASHIMA
    • Organizer
      SfN 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Modeling benign adult familial myoclonic epilepsy (BAFME) using patient specific induced pluripotent stem cells (iPSCs)- derived neurons2018

    • Author(s)
      Y. NAGASAKO, S. MAEDA, M. ISHIKAWA, H. ISHIURA, T. TODA, S. TSUJI, H. OKANO
    • Organizer
      SfN 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vitro disease modeling of the FTDP-17 TAU R406W mutation using patient-derived iPSCs2018

    • Author(s)
      M. NAKAMURA, H. WATANABE, S. SHIOZAWA, S. MAEDA, S.-I. HISANAGA3, N. SAHARA, T. KIMURA, T. MIYASAKA, A. TAKASHIMA, T. IKEUCHI, H. OKANO
    • Organizer
      SfN 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Physiological role of dendritic tau protein on AMPA receptor dynamics2018

    • Author(s)
      M. KANATANI, H. BANNAI, Y. SOEDA, S. MAEDA, A. TAKASHIMA
    • Organizer
      SfN 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Aggregation-dependent and independent pathogenesis of Tau protein2018

    • Author(s)
      Sumihiro Maeda
    • Organizer
      Keio-Cologne Symposium on Aging and Longevity
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Aggregation-dependent and independent pathogenesis of Tau protein2017

    • Author(s)
      Sumihiro Maeda
    • Organizer
      Karolinska Institute Joint Summer Program 2017 "Brain Aging"
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Aggregation-dependent and independent pathogenesis of Tau protein2017

    • Author(s)
      Sumihiro Maeda
    • Organizer
      タウ研究会2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2017-08-25   Modified: 2020-03-30  

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