β-Amyloid-induced changes in cytoskeletons and impairment of axonal transport
| Project/Area Number |
15500245
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | Kitasato University |
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Principal Investigator |
HIRUMA Hiromi Kitasato University, School of medicine, Associate Professor, 医学部, 助教授 (10238397)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | β-Amyloid / Axonal transport / Cytoskeleton / Actin filaments / Alzheimer's disease |
|---|
| Research Abstract |
Impairment of axonal transport leads to neurodegeneration and synapse loss. β-Amyloid (Aβ) has critical roles in the pathogenesis of Alzheimer's disease. The present study demonstrated that Aβ rapidly inhibited fast axonal transport in cultured rat hippocampal neurons. The effect of Aβ was progressive and irreversible, was prevented by the actin-depolymerizing agent latrunculin B, and was mimicked by the actin-polymerizing agent jasplakinolide. Aβ induced intracellular actin aggregation, which was prevented by latrunculin B. Aβ fragments Aβ_<31-35> and Aβ_<25-35> exerted the aggregation of action filaments and the inhibition of axonal transport, but Aβ_<15-20> had no effect. Aβ_<1-42> incubated for 7 days, which specifically contained 30-100 kDa molecular weight assemblies, also caused an inhibition of axonal transport associated with intracellular actin aggregation, whereas freshly dissolved Aβ_<1-40>, incubated Aβ_<1-40>, and fresh Aβ_<1-42> had no effect. These results suggest that AB inhibits axonal transport via actin polymerization and aggregation. The ability of Aβ to inhibit axonal transport seems to require active amino acid residues, which is probably present in the 31-35 sequence. Full-length Aβ may be effective when it represents a structure where these active residues can access the cell membrane. The present results may provide insight into the early pathogenetic mechanisms of Alzheimer's disease.
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Nitric oxide generated by iNOS reduces deformability of Lewis lung carcinoma cells.2004
Author(s)
Igawa, S., Hayashi, I., Tanaka, N., Hiruma, H., Majima, M., Kawakami, T., Hirose, M., Masuda, N., Kobayashi, H.
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Journal Title
Cancer Science 95(4)
Pages: 342-347
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Fatty acids as an energy source for the operation of axoplasmic transport.2003
Author(s)
Takenaka, T., Hiruma, H., Hori, H., Hashimoto, Y., Ichikawa, T., Kawakami, T.
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Journal Title
Brain Research 972(1-2)
Pages: 38-43
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Glutamate and amyloid bet, -protein rapidly inhibit fast axonal transport in cultured rat hippocampal neurons by different mechanisms.2003
Author(s)
Hiruma, H., Katakura, T., Takahashi, S., Ichikawa, T., Kawakami, T.
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Journal Title
The Journal of Neuroscience 23(26)
Pages: 8967-8977
Description
「研究成果報告書概要(欧文)」より
Related Report
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