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Glial Cell Therapy Using Neuroprotective effects of Glia

Research Project

Project/Area Number 15590078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

TANIGUCHI Takashi  Kyoto Pharmaceutical University, Pharmaceutical Sciences, Professor, 薬学部, 教授 (10111957)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsMicroglia / Astrocytes / Alzheimer's disease / Amyloid-β clearance / Phagocytosis / Rat brain focal ischemia / Cytokines / Neuroprotective effects / 熱ショック蛋白質-90
Research Abstract

Recent studies have indicated that prolonged dysfunction and/or stress in the endoplasmic reticulum (ER) may contribute to pathogenesis and neurodegeneration. The disorder caused by misfolding and aggregation of proteins has been referred to as conformational disease, including Alzheimer's disease (AD). AD is characterized by the accumulation of extracellular amyloid-β 1-42 (Aβ42) fibrils with microglia. Understanding the balance of production and clearance of Aβ42 is the key to elucidating amyloid plaque homeostasis. We have recently found that microglial phagocytosis of Aβ42 may be essentially driven by dynamic reorganization of the actin cytoskeleton through the pathway of the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) and GTP-binding protein Rac1. In addition, an extracellular stress protein, such as heat-shock protein-90 (Hsp90), enhanced Aβ42 phagocytosis. High mobility group box protein-1 (HMGB1) inhibited microglial phagocytosis of Aβ42, and it bound Aβ42 and stabilized the ologomerization. These results suggest that microglial clearance of Aβ42 may be another option for investigations in the search for a therapeutic strategy for AD. Furthermore, although occlusion of the middle cerebral artery (MCA) caused massive neuronal loss, intracerebroventricular-injected microglia migrated into brain damaged parenchyma and then protect against neurodegeneration by focal brain ischemia.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (15 results)

All 2004 2003 Other

All Journal Article (12 results) Publications (3 results)

  • [Journal Article] Intracerebroventricular injection of microglia protects against focal brain ischemia.2004

    • Author(s)
      Yoshihisa Kitamura et al.
    • Journal Title

      Journal of Pharmacological Sciences 94・2

      Pages: 203-206

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Pharmacological characteristics of rotational behavior in hemi-parkinsonian rats transplantation of mouse ES cell-derived neurons.2004

    • Author(s)
      Masatoshi Inden et al.
    • Journal Title

      Journal of Pharmacological Sciences 96・1

      Pages: 53-64

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] High mobility group box-1 inhibits microglial Aβ clearance and enhances Aβ neurotoxicity.2004

    • Author(s)
      Kazuyuki Takata et al.
    • Journal Title

      Journal of Neuroscience Research 78・6

      Pages: 880-891

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Intracerebroventricular injection of microglia protects against focal brain ischemia2004

    • Author(s)
      Yoshihisa Kitamura et al.
    • Journal Title

      Journal of Pharmacological Sciences 94(2)

      Pages: 203-206

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pharmacological characteristics of rotational behavior in hemiparkinsonian rats transplanted mouse ES cell-derived neurons2004

    • Author(s)
      Masatoshi Inden et al.
    • Journal Title

      Journal of Pharmacological Sciences 96(1)

      Pages: 53-64

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] High mobility group box protein-1 inhibits microglial Aβ clearance and enhances Aβ neurotoxicity2004

    • Author(s)
      Kazuyuki Takata et al.
    • Journal Title

      Journal of Neuroscience Research 78(6)

      Pages: 880-891

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pharmacological characteristics of rotational behavior in hemi-parkinsonian rats transplanted with mouse ES cell-derived neurons.2004

    • Author(s)
      Masatoshi Inden et al.
    • Journal Title

      Journal of Pharmacological Sciences 96・1

      Pages: 53-64

    • Related Report
      2004 Annual Research Report
  • [Journal Article] High mobility group box protein-1 inhibits microglial Aβ clearance and enhances Aβ neurotoxicity.2004

    • Author(s)
      Kazuyuki Takata et al.
    • Journal Title

      Journal of Neuroscience Research 78・6

      Pages: 880-891

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Heat shock protein-90-induced microglial clearance of exogenous amyloid-β1-42 in rat hippocampus in vivo.2003

    • Author(s)
      Kazuyuki Takata et al.
    • Journal Title

      Neuroscience Letters 344・2

      Pages: 87-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Involvement of WAVE and Rac1 in the phagocytosis of amyloid-β(1-42) in rat microglia.2003

    • Author(s)
      Yoshihisa Kitamura et al.
    • Journal Title

      Journal of Pharmacological Sciences 92・2

      Pages: 115-123

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Heat shock protein-90-induced microglial clearance of exogenous amyloid-β1-42 in rat hippocampus in vivo2003

    • Author(s)
      Kazuyuki Takata et al.
    • Journal Title

      Neuroscience Letters 344(2)

      Pages: 87-90

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Involvement of WAVE and Rac1 in the phagocytosis of amyloid-β(1-42) in rat microglia2003

    • Author(s)
      Yoshihisa Kitamura et al.
    • Journal Title

      Journal of Pharmacological Sciences 92(2)

      Pages: 115-123

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Kazuyuki Takata et al.: "Heat shock protein-90-induced microglial clearance of exogenous amyloid-β1-42 in rat hippocampus in vivo."Neuroscience Letters. 344・2. 87-90 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshihisa Kitamura et al.: "Involvement of WAVE and Rac1 in the phagocytosis of amyloid-β(1-42) in rat microglia."Journal of Pharmacological Sciences. 92・2. 115-123 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshihisa Kitamura et al.: "Intracerebroventricular injection of microglia protects against focal brain ischemia."Journal of Pharmacological Sciences. (印刷中). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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