| Project/Area Number |
11670638
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kitasato University |
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Principal Investigator |
HIRUMA Hiromi Kitasato Univ. School of Medicine, Department of Physiology, Associate Professor, 医学部, 助教授 (10238397)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | amyloid protein / hippocampus / axonal transport / Alzheimer's disease / tau phosphorylation / ニューロフィラメント |
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| Research Abstract |
Recent studies on Alzheimer's disease have suggested that β-amyloid protein is closely related to the pathogenesis of this disease. In the present study, the effect of β-amyloid protein on axonal transport of particles in neurites of cultured rat hippocampal neurons was investigated using video-enhanced microscopy. Application of β-amyolid protein_<25-35> (Aβ_<25-35>) rapidly decreased the number of particles transported in anterograde and retrograde directions. This effect was sustained during the application. When the concentration of Aβ_<25-35> was increased, the effect was irreversible and progressive. Axonal transport of mitochondria was also reduced. When Aβ_<25-35> was per fused intracellularly using patch pipettes, axonal transport was extremely reduced. The inhibitory effect of Aβ_<25-35> was blocked by the pre-treatment with butyrolactone I, a cyclin-dependent kinase 5 (Cdk5) to hyperphosphorylate tau proteins. These results indicate that β-amyloid protein inhibits axonal transport of particles including mitochondria. This effect may be induced by Cdk5-mediated phosphorylation of tau proteins. Reduction in axonal transport by β-amyloid protein may be related to the pathogenesis of Alzheimer's disease.
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