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)
| Project/Area Number |
10470095
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Kobe University |
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Principal Investigator |
SUMINO Kimiaki Kobe University, School of Medicine, Public Health, Professor, 医学部, 教授 (90030832)
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| 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)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| 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)
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| Keywords | Alzheimer's disease / aluminum / thrombin / ERAB |
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| 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.
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Report
(3 results)
Research Products
(5 results)
