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The analysis of neurodegenerative processes and changes of protein interaction of tau by mutation.

Research Project

Project/Area Number 24591711
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionOsaka University

Principal Investigator

TANAKA Toshihisa  大阪大学, 医学(系)研究科(研究院), 准教授 (10294068)

Co-Investigator(Kenkyū-buntansha) KUDO Takashi  大阪大学, 保健センター, 教授 (10273632)
MORIHARA Takashi  大阪大学, 医学(系)・研究科(研究院), 助教 (90403196)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsタウ蛋白 / リン酸化 / 認知症
Outline of Final Research Achievements

To elucidate the neurodegenerative mechanisms in FTDP-17, interaction between tau and 14-3-3 protein was investigated. Affinity between two proteins was increased in mutated tau protein than in wiled typed tau protein, however the affinity increased at the same extent in both wild typed tau and mutated tau. Then aggregation was monitored and aggregation processes were more facilitated in mutated tau than in wild typed tau, however the aggregation was completely attenuated when tau was phosphorylated. Next effects of phosphorylation of tau at Ser214 were investigated, and intracellular degradation of tau is more facilitated in S214A mutated tau-transfected cells than in wiled typed tau –transfected cells. And involvement of PSA (Puromycin sensitive aminopeptidase) was also investigated. PSA can degrade tau in vitro at only at the N-terminal site, but cannot lead to complete digestion. However attenuation of PSA activity in cultured cells, induced accumulation of tau protein.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (9 results)

All 2015 2014 2013 2012

All Journal Article (5 results) Presentation (4 results) (of which Invited: 4 results)

  • [Journal Article] アルツハイマー病の新規薬物の開発と臨床応用の可能性2015

    • Author(s)
      田中稔久、武田雅俊
    • Journal Title

      精神科治療学

      Volume: 30 Pages: 63-70

    • Related Report
      2014 Annual Research Report
  • [Journal Article] アルツハイマー病・タウオパチーとMAPキナーゼ2013

    • Author(s)
      田中稔久、武田雅俊
    • Journal Title

      Clinical Neuroscience

      Volume: 31 Pages: 719-722

    • Related Report
      2013 Research-status Report
  • [Journal Article] タウの分子病理と前頭側頭葉変性症2013

    • Author(s)
      田中稔久、武田雅俊
    • Journal Title

      老年精神医学雑誌

      Volume: 24 Pages: 1628-1632

    • Related Report
      2013 Research-status Report
  • [Journal Article] Alzheimer disease and tau protein.2012

    • Author(s)
      Tanaka T, Maruyama D, Takeda M
    • Journal Title

      Rinsho Shinkeigaku

      Volume: 52 Pages: 1171-1173

    • NAID

      130004505095

    • Related Report
      2012 Research-status Report
  • [Journal Article] アミロイド沈着、神経原線維変化と認知機能低下2012

    • Author(s)
      田中稔久、武田雅俊
    • Journal Title

      老年精神医学雑誌

      Volume: 23 Pages: 434-440

    • Related Report
      2012 Research-status Report
  • [Presentation] 認知症におけるタウの分子病理2014

    • Author(s)
      246.田中稔久
    • Organizer
      第20回近畿老年期認知症研究会
    • Place of Presentation
      リーガロイヤルNCB(大阪)
    • Year and Date
      2014-07-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] N-terminal modification of tau regulates its degradation.2013

    • Author(s)
      Tanaka T, Maruyama D, Sato M, Terada M, Takeda M.
    • Organizer
      Alzheimer's Association International Conference (AAIC2013)
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] アルツハイマー病の記憶障害—タウ蛋白異常の観点から2013

    • Author(s)
      田中稔久
    • Organizer
      第18回日本神経精神医学会
    • Place of Presentation
      千里ライフサイエンスセンター
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] アルツハイマー病とタウ蛋白2012

    • Author(s)
      田中稔久
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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