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Mechanism by which the pathogenesis of Parkinson's disease is stimulated by Gaucher's mutation.

Research Project

Project/Area Number 23659462
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

HASHIMOTO Makoto  公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 副参事研究員 (50189502)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsシヌクレイン / パーキンソン病 / ゴーシェ病 / リソソーム / オートファゴソーム
Research Abstract

We observed that axonal globules are formed in both αsynuclein (αS)- and P123H Βsynuclein (βS) transgenic mice. Lysosomal pathology was similarly observed for both αS- and P123H βS-globules, while oxidative stress was associated with the αS-globules, and to a lesser extent with the P123H βS-globules. Other pathologies, such as mitochondrial alteration and LRRK2 accumulation, were exclusively detected for αS-globules. Collectively, both αS- and P123H βS-globules were formed through similar but distinct pathogenic mechanisms.

Report

(3 results)
  • 2013 Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Research-status Report
  • Research Products

    (14 results)

All 2013 2012 2011 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (5 results) (of which Invited: 1 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Dual effects of β-synuclein on the pathogenesis of Parkinson's disease2013

    • Author(s)
      Sekigawa A, Sekiyama K, Takamatsu Y, Fujita M, Hashimoto M
    • Journal Title

      Ann Neurol

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diversity of mitochondrial pathology in a mouse model of axonal degeneration in synucleinopathies.2013

    • Author(s)
      Sekigawa A, Takamatsu Y, Sekiyama K, Takenouchi T, Sugama S, Waragai M, Fujita M, Hashimoto M
    • Journal Title

      Oxid Med Cell Longev

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diversity of mitochondrial pathology in a mouse model of axonal degeneration in synucleinopathies2013

    • Author(s)
      Sekigawa A
    • Journal Title

      Oxid Med Cell Longev.

      Volume: 2013 Pages: 817807-817807

    • DOI

      10.1155/2013/817807

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinct mechanisms of axonal globule formation in mice expressing human wild type α-synuclein or dementia with Lewy bodies-linked P123H β-synuclein2012

    • Author(s)
      Sekigawa A, Fujita M, Sekiyama K, Takamatsu Y, Hatano T, Rockenstein E, La Spada AR, Masliah E, Hashimoto M
    • Journal Title

      Mol Brain

      Volume: 5 Pages: 34-34

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Distinct mechanisms of axonal globule formation in mice expressing human wild type α-synuclein or dementia with Lewy bodies-linked P123H β-synuclein.2012

    • Author(s)
      Sekigawa A
    • Journal Title

      Mol Brain.

      Volume: 5 Issue: 1 Pages: 34-34

    • DOI

      10.1186/1756-6606-5-34

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] β-Synuclein in the pathogenesis of Parkinson’s disease and related α-synucleinopathies: Emerging roles and new directions.2012

    • Author(s)
      Hashimoto, M., La Spada, AR.
    • Journal Title

      Future Neurol.

      Volume: 7(2) Issue: 2 Pages: 155-163

    • DOI

      10.2217/fnl.12.5

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Mechanism of axonal globule formation in a mouse model of α-synucleinopathy is distinct from thatin a mouse model of β-synucleinopathy2012

    • Author(s)
      関川明生 関山一成、藤田雅代、高松芳樹、橋本款
    • Organizer
      第53回日本神経病理学会総会学術研究会
    • Place of Presentation
      新潟
    • Year and Date
      2012-06-30
    • Related Report
      2013 Final Research Report
  • [Presentation] エルドバ誘発性ジスキネジアと大脳基底核におけるシヌクレイン病理の関連性2012

    • Author(s)
      橋本款
    • Organizer
      第54回日本老年医学会学術集会
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2012-06-29
    • Related Report
      2013 Final Research Report
  • [Presentation] シヌクレインマウスの軸索腫脹病変におけるリソソーム系異常およびミトファジーの組織学的解析2011

    • Author(s)
      関川 明生、藤田 雅代、関山 一成、高松 芳樹、橋本 款
    • Organizer
      第52回日本神経病理学会総会(招待講演)
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] “Mechanism of axonal globule formation in a mouse model of α-synucleinopathy is distinct from that in a mouse model of β-synucleinopathy”

    • Author(s)
      関川明生
    • Organizer
      第53回日本神経病理学会総会学術研究会
    • Place of Presentation
      新潟
    • Related Report
      2012 Annual Research Report
  • [Presentation] エルドバ誘発性ジスキネジアと大脳基底核におけるシヌクレイン病理の関連性

    • Author(s)
      橋本款
    • Organizer
      第54回日本老年医学会学術集会(招待講演)
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Book] Alzheimer's Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets. (Suzanne De La Monte, Ed.)2011

    • Author(s)
      Sekigawa A, Fujita M, Sekiyama K, Takamatsu Y, Wei J, Hashimoto M.
    • Total Pages
      4
    • Publisher
      InTech:Rijeka
    • Related Report
      2011 Research-status Report
  • [Patent(Industrial Property Rights)] 変異型βシヌクレイントランスジェニック非ヒト動物2012

    • Inventor(s)
      橋本 款、藤田 雅代、中井 雅晶、井上 聡、津久井 通
    • Industrial Property Rights Holder
      公益財団法人東京都医学総合研究所
    • Industrial Property Number
      2006-329803
    • Filing Date
      2012-12-14
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] アディポネクチンを含む神経編成疾患の治療及び/又は予防用医薬組成物2011

    • Inventor(s)
      橋本、その他4名
    • Industrial Property Rights Holder
      橋本、その他4名
    • Industrial Property Number
      2011-274797
    • Filing Date
      2011
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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