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Research on the molecular pathogenetic mechanism of tissue-specific toxicity mediated by ALS-linked mutant SOD1

Research Project

Project/Area Number 19590987
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionAichi Medical University

Principal Investigator

NIWA Jun-ichi  Aichi Medical University, 医学部, 講師 (50378022)

Co-Investigator(Kenkyū-buntansha) 田中 章景  名古屋大学, 大学院・医学系研究科, 准教授 (30378012)
祖父江 元  名古屋大学, 大学院・医学系研究科, 教授 (20148315)
Co-Investigator(Renkei-kenkyūsha) SOBUE Gen  名古屋大学, 大学院・医学系研究科, 教授 (20148315)
TANAKA Fumiaki  名古屋大学, 大学院・医学系研究科, 准教授 (30378012)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords筋萎縮性側索硬化症(ALS) / 神経変性 / 変異SOD1 / Dorfin / タンパク質凝集 / ユビキチン化 / ジスルフィド結合 / プロテオーム / 筋萎縮性側索硬化症 / 核タンパク質 / TDP-43 / 翻訳後修飾
Research Abstract

SOD1タンパク質は内部にジスルフィド(S-S)結合を形成しうるシステイン残基を4ヶ所(6, 57, 111, 146番アミノ酸)有しており、これらのうち57番と146番が酸化され相互にS-S結合を形成してSOD1分子を安定させている。我々は、6番と111番のシステイン残基の異常な酸化が変異SOD1特異的に脳幹・脊髄で生じてタンパク質凝集を促進し、高分子複合体を形成することで運動ニューロンに毒性を発揮して、筋萎縮性側索硬化症(ALS)を引き起こしていることを見出した。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (14 results)

All 2009 2008 2007

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (2 results)

  • [Journal Article] TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases2009

    • Author(s)
      Iguchi Y, Katsuno M, Niwa J, Yamada S, Sone J, Waza M, Adachi H, Tanaka F, Nagata K, Arimura N, Watanabe T, Kaibuchi K, Sobue G.
    • Journal Title

      J Biol Chem (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dorfin ameliorates phenotypes in a transgenic mouse model of amyotrophic lateral sclerosis2009

    • Author(s)
      Sone J, Niwa J, Kawai K, Ishigaki S, Yamada S, Adachi H, Katsuno M, Tanaka F, Doyu M, Sobue G.
    • Journal Title

      J Neurosci Res (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases2009

    • Author(s)
      Iguchi Y, Katsuno M, Niwa J, Yamada S, Sone J, Waza M, Adachi H, Tanaka F, Nagata K, Arimura N, Watanabe T, Kaibuchi K, Sobue G
    • Journal Title

      J Biol Chem. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dorfin ameliorates phenotypes in a transgenic mouse model of amyotrophic lateral sclerosis2009

    • Author(s)
      Sone J, Niwa J, Kawai K, Is higaki S, Yamada S, Adachi H, Katsuno M, Tanaka F, Doyu M, Sobue G
    • Journal Title

      J Neurosci Res (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disulfide bond mediates aggregation, toxicity, and ubiquitylation of familial amyotrophic lateral sclerosis-linked mutant SOD12007

    • Author(s)
      Niwa J, Yamada S, Ishigaki S, Sone J, Takahashi M, Katsuno M, Tanaka F, Doyu M, Sobue G.
    • Journal Title

      J Biol Chem 282

      Pages: 28087-28095

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gene expressions specifically detected in motor neurons (dynactin 1, early growth response 3, acetyl-CoA transporter, death receptor 5, and cyclin C) differentially correlate to pathologic markers in sporadic amyotrophic lateral sclerosis2007

    • Author(s)
      Jiang YM, Yamamoto M, Tanaka F, Ishigaki S, Katsuno M, Adachi H, Niwa J, Doyu M, Yoshida M, Hashizume Y, Sobue G.
    • Journal Title

      J Neuropathol Exp Neurol 66

      Pages: 617-627

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiling toward understanding of ALS pathogenesis2007

    • Author(s)
      Tanaka F, Niwa J, Ishigaki S, Katsuno M, Waza M, Yamamoto M, Doyu M, Sobue G.
    • Journal Title

      Ann N Y Acad Sci 1086

      Pages: 1-10

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dorfin-CHIP chimeric proteins potently ubiquitylate and degrade familial ALS-related mutant SOD1 proteins and reduce their cellular toxicity2007

    • Author(s)
      Ishigaki S, Niwa J, Yamada S, Takahashi M, Ito T, Sone J, Doyu M, Urano F, Sobue G.
    • Journal Title

      Neurobiol Dis 25

      Pages: 331-341

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Disulfide bond mediates aggregation, toxicity, and ubiquitylation of famlial amyotrophic lateral sclerosis-linked mutant SOD1.2007

    • Author(s)
      Niwa J, Yamada S, Ishigaki S, Sone J, Takahashi M, Katsuno M, Tanaka F, Doyu M, Sobue G.
    • Journal Title

      J Biol Chem. 282

      Pages: 28087-28095

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expressions specifically detected in motor neurons(dynactin 1, early growth response 3, acetyl-CoA transporter, death receptor 5, and cyclin C)differentially correlate to pathologic markers in sporadic amyotrophic lateral sclerosis.2007

    • Author(s)
      Jiang YM, Yamamoto M, Tanaka F, shigaki S, Katsuno M, Adachi H, Niwa J, Doyu M, Yoshida M, Hashizune Y, Sobue G.
    • Journal Title

      J Neuropathol Exp Neural. 66

      Pages: 617-627

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiling toward understanding of ALS pathogenesis.2007

    • Author(s)
      Tanaka F, Niwa J, Ishigaki S, Katsuno M, Waza M, Yamamoto M, Doyu M, Sobue G.
    • Journal Title

      Ann N Y Acad Sci. 1086

      Pages: 1-10

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dorfin-CHIP chimeric proteins potently ubiquitylate and degrade familial ALS-related mutant SOD1 proteins and reduce their cellular toxicity.2007

    • Author(s)
      Ishigaki S, Niwa J, Yamada S, Takaiashi M, Ito T, Sone J, Doyu M, Urano F, Sobue G.
    • Journal Title

      Neurobiol Dis. 25

      Pages: 331-341

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 孤発性ALS病態関連分子の探索と疾患モデルの開発2008

    • Author(s)
      田中章景, 和座雅浩, 丹羽淳一, 山本正彦, 祖父江元
    • Organizer
      第49回日本神経学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-05-17
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 変異SOD1と特異的に結合するタンパク質の探索同定2007

    • Author(s)
      丹羽淳一、山田新一、曽根淳、高橋美穂、道勇学、祖父江元
    • Organizer
      第48回日本神経学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-05-17
    • Related Report
      2008 Final Research Report 2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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