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Exploration of intracellular protease property and control factors of neurosin with α-synuclein degrading activity

Research Project

Project/Area Number 20591007
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

TOKUDA Takahiko  Kyoto Prefectural University of Medicine, 医学研究科, 講師 (80242692)

Co-Investigator(Kenkyū-buntansha) WATANABE Yoshihisa  京都府立医科大学, 医学研究科, 助教 (50363990)
MIZUNO Toshiki  京都府立医科大学, 医学研究科, 准教授 (30264782)
NAKAGAWA Masanori  京都府立医科大学, 医学研究科, 教授 (50198040)
Co-Investigator(Renkei-kenkyūsha) KASAI Takashi  京都府立医科大学, 医学研究科, 助教 (70516062)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsα-シヌクレイン / ニューロシン / 酵素 / パーキンソン病 / 蛋白質分解 / セリンプロテアーゼ / 蛋白分解 / 培養細胞 / 小胞体 / GFP
Research Abstract

We investigated proteolytic activity and control factors of human neurosin using cultured cells. Heterologous expression of pre-pro-neurosin was localizedto the endoplasmic reticulum and secreted. Extracellular neurosin had protease activity and can degrade α-synuclein. Meanwhile, intracellular neurosin did not have α-synuclein -degrading activity. These findings suggest that neurosin is involved in degradation ofα-synuclein as an extracellular protease.

Report

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

    (22 results)

All 2010 2009 2008

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (7 results)

  • [Journal Article] Detection of Elevated Levels of α-Synuclein Oligomers in CSF from Parkinson's Disease Patients.2010

    • Author(s)
      Tokuda T, Qureshi MM, Ardah MT, (他6名)
    • Journal Title

      Neurology 75

      Pages: 1766-1772

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Extracellular neurosin degrades α-synuclein in cultured cells.2010

    • Author(s)
      Tatebe H, Watanabe Y, Tokuda T (他4名, 7番目)
    • Journal Title

      Neurosci Res 67

      Pages: 341-346

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential levels of α-synuclein, β-amyloid42, and tau in cerebrospinal fluids between patients with dementia with Lewy bodies and Alzheimer disease.2010

    • Author(s)
      Kasuga K, Tokutake T, Tokuda T, (他5名, 5番目)
    • Journal Title

      J Neurol Neurosurg Psychiatry 81

      Pages: 608-610

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential levels of α-synuclein, β-amyloid42, and tau in cerebrospinal fluids between patients with dementia with Lewy bodies and Alzheimer disease.2010

    • Author(s)
      Kasuga K, et al.
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: 81 Pages: 608-610

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extracellular neurosin degrades α-synuclein in cultured cells.2010

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

      Neurosci Res

      Volume: 67 Pages: 341-346

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of elevated leyels of α-synuclein oligomers in CSF from Parkinson's disease patients.2010

    • Author(s)
      Tokuda T, et al
    • Journal Title

      Neurology

      Volume: 75 Pages: 1766-1772

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CSF α-synuclein levels in dementia with Lewy bodies and Alzheimer's disease.2009

    • Author(s)
      Noguchi-Shinohara M, Tokuda T, Yoshita M,(他5名)
    • Journal Title

      Brain Res 1251

      Pages: 1-6

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased TDP-43 protein in cerebrospinal fluid of patients with amyotrophic lateral sclerosis.2009

    • Author(s)
      Kasai T, Tokuda T, Ishigami N, (他6名)
    • Journal Title

      Acta Neuropathol 117

      Pages: 55-62

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased TDP-43 protein in cerebrospinal fluid of patients with amyotrophic lateral sclerosis.2009

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

      Acta Neuropathologica 117

      Pages: 55-62

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiomyopathy in a Japanese family with the Glu61Lys transthyretin variant : a new phenotype.2009

    • Author(s)
      Noto Y, et al.
    • Journal Title

      Amyloid : The Journal of Protein Folding Disorders 16

      Pages: 99-102

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The 28-amino acid form of an APLP1-derived Abeta-like peptide is a surrogate marker for Abeta42 production in the central nervous system.2009

    • Author(s)
      Yanagida K, et al.
    • Journal Title

      EMBO Molecular Medicine 1

      Pages: 222-235

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly selective leptomeningeal amyloidosis with transthyretin variant Ala25Thr.2009

    • Author(s)
      Hagiwara K, et al.
    • Journal Title

      Neurology 72

      Pages: 1358-1360

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CSF a-synuclein levels in dementia with Lewy bodies and Alzheimer's disease.2009

    • Author(s)
      Noguchi-Shinohara M, et al.
    • Journal Title

      Brain Research 1251

      Pages: 1-6

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cleavage of normal and pathological forms of alpha-synuclein by neurosin in vitro.2008

    • Author(s)
      Kasai T, Tokuda T, Watanabe Y, (他4名)
    • Journal Title

      Neurosci Lett 436

      Pages: 52-56

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cleavage of normal and pathological forms of alpha-synuclein byneurosin in vitro.2008

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

      Neuroscience Letters 4362

      Pages: 52-56

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] ヒト髄液中のα-synuclein oligomerの検討2010

    • Author(s)
      徳田隆彦
    • Organizer
      日本神経学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-05-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] アルツハイマー病患者に対するIVIg療法の検討2009

    • Author(s)
      徳田隆彦
    • Organizer
      日本認知症学会学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2009-11-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] Neurosin によるα-synuclein 分解の解析2009

    • Author(s)
      建部陽嗣, 渡邊義久, 笠井高士, 徳田隆彦, 水野敏樹, 田中雅樹, 中川正法
    • Organizer
      日本神経科学大会(第32回)
    • Place of Presentation
      名古屋
    • Year and Date
      2009-09-18
    • Related Report
      2010 Final Research Report
  • [Presentation] α-synuclein 分解酵素であるneurosin の細胞内動態の検討2009

    • Author(s)
      笠井高士, 建部陽嗣, 徳田隆彦, 石神紀子, 水野敏樹, 中川正法, 渡邊義久, 田中雅樹
    • Organizer
      日本神経学会総会(第50回)
    • Place of Presentation
      仙台
    • Year and Date
      2009-05-20
    • Related Report
      2010 Final Research Report
  • [Presentation] 筋萎縮性側索硬化症(ALS)患者の髄液中TDP-43の定量2009

    • Author(s)
      徳田隆彦
    • Organizer
      日本神経学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2009-05-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] α-Synuclein 分解酵素であるneurosin の細胞内動態の検討2009

    • Author(s)
      笠井高士, 建部陽嗣, 徳田隆彦, 渡邊義久, 田中雅樹
    • Organizer
      カテコールアミンと神経疾患研究会(第17回)
    • Place of Presentation
      東京
    • Year and Date
      2009-04-18
    • Related Report
      2010 Final Research Report
  • [Presentation] CJD 患者髄液中ではα-synuclein の断片ペプチドが増加している2008

    • Author(s)
      笠井高士, 徳田隆彦, 石神紀子, 中川正法, 坪井義夫
    • Organizer
      日本認知症学会学術集会(第27回)
    • Place of Presentation
      前橋
    • Year and Date
      2008-10-10
    • Related Report
      2010 Final Research Report

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

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