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Analyses on the mode of proteolysis and aggregation of synphilin-1 that constitutes the core of Lewy bodies

Research Project

Project/Area Number 21591085
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionHiroshima University

Principal Investigator

TAKAHASHI Tetsuya  広島大学, 病院, 講師 (00435942)

Co-Investigator(Kenkyū-buntansha) MATSUMOTO Masayasu  広島大学, 大学院・医歯薬学総合研究科, 教授 (20192346)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脳神経疾患 / 神経科学 / 蛋白質 / たんぱく質
Research Abstract

Impairments in the proteolytic process of disease-specific proteins have been assumed to be the cause of the formation of neuronal inclusions and subsequent neuronal cell death. In Parkinson' s disease, Synphilin-1 is one of the constituents of Lewy bodies that characterize Parkinson' s disease pathologically. We hypothesized that the perturbation of intracellular vesicle trafficking is the underlying cause which leads to the formation of neuronal inclusion, and elucidated that ESCRT(endosomal sorting complex required for transport) pathway is implicated in the Lewy bodies formation. We also demonstrated that ubiquitination of Synphilin-1 by Siah-1 is a signal that recruit Synphilin-1 to ESCRT pathway.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (30 results)

All 2011 2010 2009

All Journal Article (20 results) (of which Peer Reviewed: 18 results) Presentation (10 results)

  • [Journal Article] Granulo vacuolar degenerations appear in relation to hippocampal phosphorylated tau accumulation in various neurode generative disorders2011

    • Author(s)
      Yamazaki Y, Matsubara T, Takahashi T, Kurashige T, Dohi E, Hiji M, NaganoY, Yamawaki T, Matsumoto M.
    • Journal Title

      PLoS One

      Volume: 6(11)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lifetime risk of stroke and impact of hypertension : estimates from the adult health study in Hiroshima and Nagasaki2011

    • Author(s)
      Takahashi I, Geyer SM, Nishi N, Ohshita T, Takahashi T, Akahoshi M, Fujiwara S, Kodama K, Matsumoto M.
    • Journal Title

      Hypertens Res

      Volume: 34(5) Pages: 649-54

    • NAID

      10031163232

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Simulated Microgravity Maintains the Undifferentiated State and Enhances the Neural Repair Potential of Bone Marrow Stromal Cells2011

    • Author(s)
      Yuge L, Sasaki A, Kawahara Y, Wu SL, Matsumoto M, Manabe T, Kajiume T, Takeda M, Magaki T, Takahashi T, Kurisu K, Matsumoto M.
    • Journal Title

      Stem Cells Dev

      Volume: 20(5) Pages: 893-900

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Granulovacuolar degenerations appear in relation to hippocampal phosphorylated tau accumulation in various neurodegenerative disorders2011

    • Author(s)
      Yamazaki Y, et al
    • Journal Title

      PLoS One

      Volume: 6(CD-ROM) Issue: 11 Pages: e26996-e26996

    • DOI

      10.1371/journal.pone.0026996

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simulated microgravity maintains the undifferentiated state and enhances the neural repair potential of bone marrow stromal cells2011

    • Author(s)
      Yuge L, et al
    • Journal Title

      Stem Cells Dev

      Volume: 20 Issue: 5 Pages: 893-900

    • DOI

      10.1089/scd.2010.0294

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lifetime risk of stroke and impact of hypertension : estimates from the adult health study in Hiroshima and Nagasaki2011

    • Author(s)
      Takahashi I, et al
    • Journal Title

      Hypertens Res

      Volume: 34 Issue: 5 Pages: 649-654

    • DOI

      10.1038/hr.2011.7

    • NAID

      10031163232

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The pathophysiology of prospective memory failure after diffuse axonal injury-lesion-symptom analysis using diffusion tensor imaging2010

    • Author(s)
      Kondo K, Maruishi M, Ueno H, SawadaK, Hashimoto Y, Ohshita T, TakahashiT, Ohtsuki T, Matsumoto M.
    • Journal Title

      BMC Neurosci

      Volume: 11 Pages: 147-147

    • NAID

      120002753723

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunopositivity for ESCRT-IIIsubunit CHMP2B in granulovacuolar degeneration of neurons in the Alzheimer' s disease hippocampus2010

    • Author(s)
      Yamazaki Y, Takahashi T, Hiji M, Kurashige T, Izumi Y, Yamawaki T, Matsumoto M.
    • Journal Title

      Neurosci Lett

      Volume: 477(2) Pages: 86-90

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of Herp facilitates degradation of cytosolic proteins2010

    • Author(s)
      Miura H, Hashida K, Sudo H, Awa Y, Takarada-Iemata M, Kokame K, Takahashi T, Matsumoto M, Kitao Y, Hori O.
    • Journal Title

      Genes Cells

      Volume: 15(8) Pages: 843-53

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] SakaiN. Mutant protein kinase C gamma that causes spinocerebellar ataxia type 14(SCA14) is selectively degraded by autophagy2010

    • Author(s)
      Yamamoto K, Seki T, Adachi N, Takahashi T, Tanaka S, Hide I, Saito N.
    • Journal Title

      Genes Cells

      Volume: 15(5) Pages: 425-38

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunopositivity for ESCRT-III subunit CHMP2B in granulovacuolar degeneration of neurons in the Alzheimer's disease hippocampus2010

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

      Neurosci Lett

      Volume: 477 Pages: 86-90

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of Herp facilitates degradation of cytosolic proteins2010

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

      Genes Cells

      Volume: 15 Pages: 843-853

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutant protein kinase C gamma that causes spinocerebellar ataxia type 14 (SCA14) is selectively degraded by autophagy2010

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

      Genes Cells

      Volume: 15 Pages: 425-438

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunopositivity for ESCRT-III subunit CHMP2B in granulovacuolar de generation of neurons in the Alzheimer's disease hippocampus2010

    • Author(s)
      Yamazaki, Takahashi, et al.
    • Journal Title

      Neuroscience Letters (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association betweencentral systolic blood pressure, whitematter lesions in cerebral MRI and carotid atherosclerosis2009

    • Author(s)
      Shrestha I, Takahashi T, Nomura E, Ohtsuki T, Ohshita T, Ueno H, Kohriyama T, Matsumoto M.
    • Journal Title

      Hypertens Res

      Volume: 32 : 8 Pages: 69-74

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 新規GFAP遺伝子変異(S398F)を認めた成人型Alexander病の1例2009

    • Author(s)
      末田芳雅, 高橋哲也, 越智一秀, 大槻俊輔, 滑川道人, 郡山達男, 瀧山嘉久, 松本昌泰
    • Journal Title

      臨床神経

      Volume: 49(6) Pages: 358-63

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diagonal ear-lobe crease is correlated with at herosclerotic changes in carotid arteries2009

    • Author(s)
      Isha S, Ohtsuki T, Takahashi T, Nomura E, Kohriyama T, Matsumoto M
    • Journal Title

      Circulation J

      Volume: 73 Pages: 1945-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 新規GFAP遺伝子変異(S398F)を認めた成人型 Alexander 病の1例2009

    • Author(s)
      末田芳雅, 高橋哲也, ら
    • Journal Title

      臨床神経学 49

      Pages: 358-363

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 脳梗塞の分子病態と標的分子2009

    • Author(s)
      高橋哲也, 松本昌泰
    • Journal Title

      実験医学 27

      Pages: 949-954

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 脳血管障害のゲノミックス2009

    • Author(s)
      高橋哲也, 松本昌泰
    • Journal Title

      老年精神医学雑誌 20

      Pages: 980-988

    • Related Report
      2009 Annual Research Report
  • [Presentation] 顆粒空胞変性は神経原線維変化の随伴所見か2011

    • Author(s)
      高橋哲也、倉重毅志、山崎雄、日地正典、山脇健盛、松本昌泰
    • Organizer
      第52回日本神経学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] 顆粒空胞変性は神経原線維変化の随伴所見か?2011

    • Author(s)
      高橋哲也
    • Organizer
      第52回日本神経学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Presentation] Granulovacuolar degenerations areassociated with taupathology2010

    • Author(s)
      Tomoyasu Matsubara, TetsuyaTakahashi, Takashi Kurashige, YuuYamazaki, Masanori Hiji, YuishinIzumi, Takemori Yamawaki, Masayasu Matsumoto
    • Organizer
      International congress ofneuropathology
    • Place of Presentation
      Salzburg, Austria
    • Related Report
      2011 Final Research Report
  • [Presentation] 後骨間神経に「くびれ」を呈し、神経剥離術が有効であった1症例2010

    • Author(s)
      高橋哲也、砂川融、越智一秀、山脇健盛、郡山達男、松本昌泰
    • Organizer
      第28回日本神経治療学会
    • Place of Presentation
      横浜
    • Related Report
      2011 Final Research Report
  • [Presentation] Immunopositivity for ESCRT-III subunit CHMP2B in granulovacuolar degeneration of neurons in the Alzheimer's disease hippocampus2010

    • Author(s)
      Yamazaki Y, et al.
    • Organizer
      XVIIth International Congress of Neuropathology
    • Place of Presentation
      オーストリア
    • Related Report
      2010 Annual Research Report
  • [Presentation] Granulovacuolar degenerations are associated with taupathology2010

    • Author(s)
      Matsubara T, et al.
    • Organizer
      XVIIth International Congress of Neuropathology
    • Place of Presentation
      オーストリア
    • Related Report
      2010 Annual Research Report
  • [Presentation] ESCRT pathway is involved in the formation of Lewy body and Glial cytoplasmic inclusion2010

    • Author(s)
      Kurashige T, et al.
    • Organizer
      XVIIth International Congress of Neuropathology
    • Place of Presentation
      オーストリア
    • Related Report
      2010 Annual Research Report
  • [Presentation] 運動ニューロン病におけるエンドソーム関連蛋白の免疫染色性2009

    • Author(s)
      高橋哲也, ら
    • 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] パーキンソン病患者におけるGERD(gastro-esophagealreflux disease)有病率について2009

    • Author(s)
      高橋哲也
    • Organizer
      第3回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] 運動ニューロン病におけるエンドソーム関連蛋白の免疫染色性2009

    • Author(s)
      高橋哲也、日地正典、郡山達男、松本昌泰
    • Organizer
      第50回日本神経学会総会
    • Place of Presentation
      仙台
    • Related Report
      2011 Final Research Report

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

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