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Studies of an early stage amyloid formation for Parkinson`s Disease casual protein.

Research Project

Project/Area Number 20550083
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Analytical chemistry
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

TASHIRO Sakurako  Tokyo University of Pharmacy and Life Science, 薬学部, 講師 (40328555)

Co-Investigator(Kenkyū-buntansha) KOJIMA Masaki  東京薬科大学, 生命科学部, 教授 (90277252)
TASHIRO Mitsuru  明星大学, 理工学部, 准教授 (40315750)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords生物学的分析 / a-synuclein / アミロイド線維 / パーキンソン病 / ドパミン / オリゴマー中間体 / 高分子構造・物性 / アミロイド / 脳神経疾患 / 生理物理 / 分析化学 / 生物物理
Research Abstract

In this study, we have focused on α-synuclein, the major component of amyloid plaque in Parkinson's Disease (PD). The relationship between a detailed mechanism of amyloid formations and PD has been investigated. In particular, an interaction between α-synuclein and dopamine, a neurotransmitter and well known treatment for PD, has been elucidated in terms of its effect on amyloid formation, using fluorescence, CD, gelfilteration chromatography, NMR and MS. As a result, we have shown that the presence of dopamine suppresses the formation of amyloid fibrils, while theformation of oligomer intermediates is stabilized by addition of dopamine. Furthermore, the complex formation between α-synuclein and dopamine has been confirmed, with a binding ratio of 1 to 3 dopamine molecules per α-synuclein molecule. In conclusion, we have proposed a schematic model for the mechanism of α-synuclein oligomer intermediates and amyloid formations.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (21 results)

All 2010 2009 2008 Other

All Journal Article (8 results) (of which Peer Reviewed: 3 results) Presentation (12 results) Remarks (1 results)

  • [Journal Article] An Effective Pulse Sequence for Detecting a Ligand Binding with a Protein Receptor Using a WET Sequence and the Repeated A-Filters"2010

    • Author(s)
      Furihata Kazuo ; Shimotakahara Sakurako ; Shibusawa Yoichi ; Tashiro Mitsuru
    • Journal Title

      Anal.Sic. 26

      Pages: 1107-1110

    • Related Report
      2010 Final Research Report
  • [Journal Article] An Effective Pulse Sequence for Detecting a Ligand Binding with a Protein Receptor Using a WET Sequence and the Repeated A-Filters2010

    • Author(s)
      Furihata, Kazuo ; Shimotakahara, Sakurako ; Shibusawa, Yoichi ; Tashiro, Mitsuru
    • Journal Title

      Analytical Science

      Volume: 26 Pages: 1107-1111

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Application of WET sequence for the detection of the ligand signals resonating close to water2009

    • Author(s)
      Furihata Kazuo ; Shimotakahara Sakurako ; Shibusawa Yoichi ; Tashiro Mitsuru
    • Journal Title

      Magn Reson Chem 47(11)

      Pages: 971-976

    • Related Report
      2010 Final Research Report
  • [Journal Article] Application of WET sequence for the detection of the ligand signals resonating close to water2009

    • Author(s)
      Furihata, Kazuo, Shimotakahara, Sakurako, Shibusawa, Yoichi, Tashiro, Mitsuru
    • Journal Title

      Magnetic Resonance in Chemistry 47

      Pages: 971-976

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An efficient use of the WATERGATE W5 sequence for observing a ligand binding with a protein receptor.2008

    • Author(s)
      Furihata K, Shimotakahara S, Tashiro M.
    • Journal Title

      Magn Reson Chem.Jun 6

    • Related Report
      2010 Final Research Report
  • [Journal Article] Review : Protein Sample Preparation for Structural Biology2008

    • Author(s)
      Shimotakahara (Tashiro) S.
    • Journal Title

      Bunseki 4

      Pages: 178-182

    • Related Report
      2010 Final Research Report
  • [Journal Article] Characterization of fibrillation process of alpha-synuclein at the initial stage.2008

    • Author(s)
      Tashiro M, Kojima M, Kihara H, Kasai K, Kamiyoshihara T, Ueda K, Shimotakahara S.
    • Journal Title

      Biochem Biophys Res Commun. 369(3)

      Pages: 910-914

    • Related Report
      2010 Final Research Report
  • [Journal Article] An efficient use of the WATERGATE W5 sequence for observing a ligand binding with a protein receptor2008

    • Author(s)
      Furihata, Kazuo, Shimotakahara, Sakurako, Tashiro, Mitsuru
    • Journal Title

      Magnetic Resonance in Chemistry 46

      Pages: 799-802

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] α-Synucleinアミロイド形成初期段階におけるオリゴマー中間体に対するドパミンの寄与とその構造的特徴についての解析2010

    • Author(s)
      城山祐樹,尾上貴也,赤井麻衣,田代充,上田健二,吉田清香,関宏子,渋沢庸一,田代(下高原)櫻子
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2010 Final Research Report
  • [Presentation] a-Synucleinアミロイド形成初期段階におけるオリゴマー中間体に対するドパミンの寄与とその構造的特徴についての解析2010

    • Author(s)
      城山祐樹, 尾上貴也, 赤井麻衣, 田代充, 上田健二, 吉田清香, 関宏子, 渋沢庸一, 田代(下高原), 櫻子
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] α-Synucleinアミロイド化反応におけるオリゴマー中間体の構造解析2010

    • Author(s)
      城山祐樹,尾上貴也,赤井麻衣,吉田清香,関宏子,田代充,渋沢庸一,田代(下高原)櫻子
    • Organizer
      第54回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Year and Date
      2010-10-02
    • Related Report
      2010 Final Research Report
  • [Presentation] a-Synucleinアミロイド化反応におけるオリゴマー中間体の構造解析2010

    • Author(s)
      城山祐樹, 尾上貴也, 赤井麻衣, 吉田清香, 関宏子, 田代充, 渋沢庸一, 田代(下高原), 櫻子
    • Organizer
      第54回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Year and Date
      2010-10-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] 質量分析を用いたα-Synucleinアミロイド形成機構の解析2010

    • Author(s)
      吉田清香,田代(下高原)櫻子,城山祐樹,坂本茂,上田健二,渋沢庸一,田代充,関宏子
    • Organizer
      日本分析化学会第59年会
    • Place of Presentation
      仙台
    • Year and Date
      2010-09-15
    • Related Report
      2010 Final Research Report
  • [Presentation] 質量分析を用いたa-Synucleinアミロイド形成機構の解析2010

    • Author(s)
      吉田清香, 田代(下高原), 櫻子, 城山祐樹, 坂本茂, 上田健二, 渋沢庸一, 田代充, 関宏子
    • Organizer
      日本分析化学会第59年会
    • Place of Presentation
      仙台
    • Year and Date
      2010-09-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] α-Synucleinアミロイド形成初期段階におけるオリゴマー中間体の構造解析2010

    • Author(s)
      城山祐樹,原田卓哉,坂本茂,田代充,上田健二,渋沢庸一,田代(下高原)櫻子
    • Organizer
      日本薬学会 第132年会
    • Place of Presentation
      岡山
    • Year and Date
      2010-03-30
    • Related Report
      2010 Final Research Report
  • [Presentation] α-Synucleinアミロイド形成初期段階におけるオリゴマー中間体の構造解析2010

    • Author(s)
      城山祐樹, 原田卓哉, 坂本茂, 田代充, 上田健二, 澁澤庸一, 下高原櫻子
    • Organizer
      第130回日本薬学会
    • Place of Presentation
      岡山
    • Year and Date
      2010-03-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] 質量分析を用いたα-Synucleinアミロイド形成初期段階のオリゴマーな中間体の構造解析2009

    • Author(s)
      城山祐樹,原田卓哉,藤本崇,田代充,上田健二,町並智也,渋沢庸一,田代(下高原)櫻子
    • Organizer
      日本分子生物学会 第32回年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-09
    • Related Report
      2010 Final Research Report
  • [Presentation] Structural analysis of oligomeric intermediate in initial stage of α-synuclein amyloidgenesis by mass spectrometry.2009

    • Author(s)
      城山祐樹, 原田卓哉, 藤本崇, 田代充, 上田健二, 町並智也, 澁澤庸一, 下高原櫻子
    • Organizer
      第32回日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] パーキンソン病原因タンパク質α-synucleinの初期段階アミロイド形成機構の解明2008

    • Author(s)
      笠井恒希,田代充,小島正樹,木原裕,上田健治,上吉原智晃,田代(下高原)櫻子
    • Organizer
      第31回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-09
    • Related Report
      2010 Final Research Report
  • [Presentation] パーキンソン病原因タンパク質a-synucleinの初期段階アミロイド形成機構の解明2008

    • Author(s)
      笠井恒希, 田代充, 小島正樹, 木原裕, 上田健治, 上吉原智晃, 田代(下高原)櫻子
    • Organizer
      第31回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-09
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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