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Investigation of pathophysiological mechanisms of synucleinopathy using cultured cellular model

Research Project

Project/Area Number 21790831
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionTohoku University

Principal Investigator

KOBAYASHI Michiko  Tohoku University, 大学院・医学系研究科, 非常勤講師 (40422109)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsシヌクレイノパチー / シヌクレイン / 多系統萎縮症 / 異常タンパク凝集 / 細胞モデル / TPPP/p25 / GCI / オリゴデンドログリア / Sirtuin / αシヌクレイン / レビー小体 / TPPP / p25 / アグレソーム / 細胞死 / アポトーシス / SIRT2
Research Abstract

To clarify the molecular mechanisms of GCI formation and subsequent oligodendroglial degeneration, we ectopically expressed α-SYN and TPPP in HEK293T and oligodendroglial KG1C cell lines. Here we showed that TPPP specifically accelerated α-SYN oligomer formation and co-immunoprecipitation analysis revealed the specific interaction of TPPP and α-SYN. Moreover, phosphorylation of α-SYN at Ser-129 facilitated the TPPP-mediated α-SYN oligomerization. TPPP facilitated α-SYN-positive cytoplasmic perinuclear inclusions mimicking GCI in both cell lines ; however, apoptotic cell death was only observed in KG1C cells. This apoptotic cell death was partly rescued by sirtuin 2 inhibition.

Report

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

    (16 results)

All 2010 2009 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (6 results) Remarks (1 results)

  • [Journal Article] Role of TPPP/p25 on alpha-synuclein-mediated oligodendroglial degeneration and the protective effect of SIRT2 inhibition in a cellular model of multiple system atrophy.2010

    • Author(s)
      Hasegawa T, Baba T, Kobayashi M, Konno M, Sugeno N, Kikuchi A, Itoyama Y, Takeda A
    • Journal Title

      Neurochem Int 57

      Pages: 857-66

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo visualization of alpha-synuclein deposition by carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl ]-6-[2-(fluoro)ethoxy benzoxazole positron emission tomography in multiple system atrophy.2010

    • Author(s)
      Kikuchi A, Takeda A, Okamura N, Tashiro M, Hasegawa T, Furumoto S, Kobayashi M, Sugeno N, Baba T, Miki Y, Mori F, Wakabayashi K, Funaki Y, Iwata R, Takahashi S, Fukuda H, Arai H, Kudo Y, Yanai K, Itoyama Y.
    • Journal Title

      Brain 133

      Pages: 1772-1778

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of TPPP/p25 on alpha-synuclein-mediated oligodendroglial degeneration and the protective effect of SIRT2 inhibition in a cellular model of multiple system atrophy.2010

    • Author(s)
      Hasegawa T, et al.
    • Journal Title

      Neurochemisty International

      Volume: 57 Pages: 857-866

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tyrosinase-expressing neuronal cell line as in vitro model of Parkinson's disease.2010

    • Author(s)
      Hasegawa T, et al.
    • Journal Title

      Int J Mol Sci

      Volume: 11 Pages: 1082-1089

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo visualization of alpha-synuclein deposition by carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy]benzox azole positron emission tomography in multiple system atrophy2010

    • Author(s)
      Kikuchi A, et al
    • Journal Title

      Brain

      Volume: 133 Pages: 1772-1778

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tyrosinase-expressing neuronal cell line as in vivo model of Parkinson's disease2010

    • Author(s)
      Hasegawa T, et al.
    • Journal Title

      Int J Mol Sci 11

      Pages: 1082-9

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional imaging studies of hyposmia in Parkinson's disease2010

    • Author(s)
      Takeda A, et al.
    • Journal Title

      J Neurol Sci 15

      Pages: 36-9

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Parkin protects Mitochondrial Genome Integrity and supports Mitochondrial DNA Repair2009

    • Author(s)
      Rothfuss O, et al.
    • Journal Title

      Hum Mol Genet 18

      Pages: 3832-50

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nuclear and neuritic distribution of serine-129 phosphorylated alpha-synuclein in transgenic mice2009

    • Author(s)
      Schell H, et al.
    • Journal Title

      Neuroscience 160

      Pages: 796-804

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] αシヌクレイン分泌・ライソゾーム移行を制御する細胞内膜動輸送系の探索2010

    • Author(s)
      長谷川隆文、馬場徹、小林理子、菅野直人、菊池昭夫、武田篤糸山泰人
    • Organizer
      日本パーキンソン病・運動障害疾患学会(Movement Disorder Society Japan ; MDSJ) 2010
    • Place of Presentation
      京都
    • Year and Date
      2010-10-07
    • Related Report
      2010 Final Research Report
  • [Presentation] αシヌクレイン分泌ライソゾーム移行を制御する細胞内膜動輸送系の探索2010

    • Author(s)
      長谷川隆文, ほか
    • Organizer
      MDSJ2010
    • Place of Presentation
      京都
    • Year and Date
      2010-10-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] 細胞内へのα-synuclein取り込み機構の解析2010

    • Author(s)
      長谷川隆文、馬場徹、小林理子、菅野直人、菊池昭夫、武田篤、糸山泰人
    • Organizer
      第51回神経学会学術大
    • Place of Presentation
      東京
    • Year and Date
      2010-05-22
    • Related Report
      2010 Final Research Report
  • [Presentation] 細胞内へのα-synuclein取り込み機構の解析2010

    • Author(s)
      長谷川隆文, ほか
    • Organizer
      第51回神経学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2010-05-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] GCI形成過程における Tubulin polymerization promoting protein の機能的役割2009

    • Author(s)
      小林理子
    • Organizer
      第50回日本神経学会総会(仙台)
    • Place of Presentation
      仙台市
    • Year and Date
      2009-05-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] GCI形成過程におけるTubulin polymerization promoting proteinの機能的役割2009

    • Author(s)
      長谷川隆文、馬場徹、小林理子、菅野直人、菊池昭夫、武田篤、糸山泰人
    • Organizer
      第50回日本神経学会総会
    • Place of Presentation
      仙台
    • Related Report
      2010 Final Research Report
  • [Remarks] 以下の東北大学神経内科教室のホームページにおいても、本研究結果の概要を提示している

    • URL

      http://www.neurol.med.tohoku.ac.jp/

    • Related Report
      2010 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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