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アルツハイマー病アミロイド・ベーター蛋白の毒性発現の抑制機構(メタロチオネイン及びその類似蛋白とアルミニウムの影響)

Research Project

Project/Area Number 10470095
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionKobe University

Principal Investigator

SUMINO Kimiaki  Kobe University, School of Medicine, Public Health, Professor, 医学部, 教授 (90030832)

Co-Investigator(Kenkyū-buntansha) LEE Myeong,jim  Kobe University, School of Medicine, Public Health, Associate Professor, 医学部, 助手 (20273766)
NISHIO Hisahide  Kobe University, School of Medicine, Public Health, Associate Professor, 医学部, 助教授 (80189258)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsAlzheimer's disease / aluminum / thrombin / ERAB
Research Abstract

Senile plaques are a major pathological hallmark of Alzheimer's disease (AD). They contain β-amyloid protein (βA), derived from amyloid precursor protein (APP). βA is thought to contribute to the pathogenesis of the disease, but the mechanism of its neurotoxicity remains unknown. Accumulated aluminum and thrombin have been expected to predispose βA to a toxic cause in neurons. Recently, an intracellular protein that binds βA and mediates neurotoxicity in AD, ERAB (endoplasmic-reticulum-associated binding protein), has been identified. To find a method to induce ERAB in neuronal cells. In the first fiscal year (1998), to determine whether aluminum induces ERAB mRNA, we grew neuroblastoma cells (GOTO) in serum-free RPMI 1640 medium containing aluminum sulfate (500μM) for 12 hours. The cells exposed to aluminum sulfate showed significantly lower APP mRNA level than the control cells. However, the cells exposed to aluminum sulfate showed no significant change in ERAB mRNA level, indicating that aluminum does not induce ERAB mRNA. In the second fiscal year (1999), to determine whether thrombin receptor activation induces ERAB mRNA, we grew neuroblastoma cells (GOTO) in serum-free RPMI 1640 medium containing TRAP (thrombin receptor activating peptide) (100μM) for 12 hours. The cells exposed to TRAP showed significantly higher APP mRNA level than the control cells. However, the cells exposed to TRAP showed no significant change in ERAB mRNA level, indicating that thrombin receptor activation does not induce ERAB mRNA. In conclusion, neither aluminum nor thrombin induces ERAB mRNA, suggesting that they do not relate to the pathogenesis of AD via ERAB mRNA induction.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report

Research Products

(5 results)

All Other

All Publications (5 results)

  • [Publications] Hisahide Nishino et al.: "High incidence of a survival motor neuron gene/cBCD541 gene ratio of 2 in Japanese Parents of spinal muscular atrophy patients : a characteristic background of spinal muscular atrophy in Japan?"J. Neuro. 246 (1). 48-52 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hisahide Nishino et al.: "Hybrid survival motor neuron genes in Japanese patients with spinal muscular atrophy"Acta Neurological Scandinavica. 99 (6). 374-380 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] "Japanese patient with spinal muscular atrophy"Acta Neurologica Scandinavica. 99(6). 374-380 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hisahide Nishio et al: "High incidence of a survival motor neuron gene/^cBCD541 gene ratio of 2 in Japanese Parents of spinal muscular atrophy patients: a characteristic background of spinal muscular atrophy in Japan?"J Neuro. 246(1). 48-52 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hisahide Nishio et al: "Hybrid survial motor neuron genes in Japanese patients with spinal muscular atrophy"Acta Neurologica Scandinavica. 99(6). 374-380 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1998-03-31   Modified: 2016-04-21  

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