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Research for drug effectiveness in Alexander disease model

Research Project

Project/Area Number 24591273
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

YOSHIDA Tomokatsu  京都府立医科大学, 医学(系)研究科(研究院), 講師 (90457987)

Co-Investigator(Kenkyū-buntansha) MIZUTA Ikuko  京都府立医科大学, 大学院医学研究科・神経内科, 講師 (80397760)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsアレキサンダー病 / GFAP / アストロサイト / トランスクリプトーム解析 / 神経内科学 / 分子遺伝学
Outline of Final Research Achievements

Alexander disease is a neurodegenerative disorder, in which the genetic mutation of glial fibrillary acidic protein (GFAP), which is specifically expressed in astrocytes, is observed. To study the contribution of GFAP gene mutation to this disease, we applied three kinds of investigation as follows. 1) We established a stable astrocyte cell strain expressing wild or mutant GFAP and, then, applied transcriptome analysis using RNAseq method following drug screening. 2) We applied drug screening and climbing assay to mutant GFAP inducing drosophila model. 3) We applied microarray analysis to astrocytes derived from hippocampus in mutant GFAP mice model. At present, 1) and 3) are under analysis. As for 2), we applied drug screening using four kinds of drugs and performed climbing assay. However, neither improvement of abnormal compound eye structure nor change of the speed of climbing assay was found.

Report

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

    (15 results)

All 2015 2014 2013 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Invited: 1 results) Book (4 results)

  • [Journal Article] Characteristic abnormal signals in medulla oblongata-“eye spot” sign: four cases of elderly-onset Alexander disease.2015

    • Author(s)
      Yoshida T, Mizuta I, Saito K, Kimura Y, Park K, Ito Y, Haji S, Nakagawa M, Mizuno T.
    • Journal Title

      Neurology clinical practice

      Volume: - Issue: 3 Pages: 259-262

    • DOI

      10.1212/cpj.0000000000000124

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effects of a polymorphism in the GFAP promoter on age of onset and ambulatory disability in late-onset Alexander disease.2013

    • Author(s)
      Yoshida T, Mizuta I, Saito K, et al.
    • Journal Title

      Journal of Human Genetics

      Volume: 58 Issue: 9 Pages: 635-638

    • DOI

      10.1038/jhg.2013.83

    • NAID

      10031195302

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 小児期発症が疑われ,長期間進行停止後に増悪したと考えられたAlexander病の1例.2013

    • Author(s)
      永石彰子,中根俊成,福留隆泰,松尾秀徳,吉田誠克.
    • Journal Title

      臨床神経

      Volume: 53 Pages: 474-477

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical aspects and pathology of Alexander disease, and morphological and functional alteration of astrocyte induced by GFAP mutation2011

    • Author(s)
      Yoshida T, Nakagawa M
    • Journal Title

      Neuropathology

      Volume: 32 Issue: 4 Pages: 440-446

    • DOI

      10.1111/j.1440-1789.2011.01268.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 延髄前部のMRI異常信号は成人期発症アレキサンダー病の特徴的な所見である2014

    • Author(s)
      吉田誠克,水田依久子,斉藤光象,中川正法, 木村康義,朴貴瑛,伊藤康男,椎裕章,高橋義秋,井手俊宏,土師正太郎,水野敏樹.
    • Organizer
      第55回日本神経学会総会学術大会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2014-05-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] アレキサンダー病の臨床診断指針に対する有用性の検討.

    • Author(s)
      吉田誠克,水田依久子,斉藤光象,中川正法.
    • Organizer
      第54回日本神経学会学術大会.
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 成人型アレキサンダー病の2例.

    • Author(s)
      高橋義秋,香西由子,奈良井恒,大森信彦,真邊泰宏,吉田誠克.
    • Organizer
      第54回日本神経学会学術大会.
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] アレキサンダー病におけるGFAPプロモーター遺伝子多型解析

    • Author(s)
      吉田誠克
    • 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
  • [Presentation] Alexander病の病態:GFAP遺伝子変異がアストロサイトにもたらす形態・機能異常

    • Author(s)
      吉田誠克
    • Organizer
      第6回Brain Science Conference
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] アレキサンダー病の臨床診断指針に対する有用性の検討

    • Author(s)
      吉田誠克
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 変異GFAP遺伝子導入SW13細胞質異常凝集体の同定はアレキサンダー病の診断に有用である

    • Author(s)
      齋藤光象
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Book] 別冊 日本臨床 新領域別症候群シリーズ No.26 神経症候群(第2版) III2014

    • Author(s)
      吉田誠克
    • Total Pages
      4
    • Publisher
      日本臨牀社
    • Related Report
      2014 Annual Research Report
  • [Book] 別冊 日本臨床 新領域別症候群シリーズ No.26 神経症候群(第2版) IV2014

    • Author(s)
      吉田誠克
    • Total Pages
      5
    • Publisher
      日本臨牀社
    • Related Report
      2014 Annual Research Report
  • [Book] 神経症候群III2014

    • Author(s)
      吉田誠克
    • Total Pages
      3
    • Publisher
      日本臨牀社
    • Related Report
      2013 Research-status Report
  • [Book] 神経症候群IV2014

    • Author(s)
      吉田誠克
    • Total Pages
      3
    • Publisher
      日本臨牀社
    • Related Report
      2013 Research-status Report

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

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