2001 Fiscal Year Final Research Report Summary
Mebiianism of neuronal cell death in Alzheimer disease. - AD analysis of signal transduction.
| Project/Area Number |
11670617
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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 | Fukui Medical University |
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Principal Investigator |
KURIYAMA Masaru Fukui Medical University.Umversity HoSpital,Professsor, 医学部, 教授 (80107870)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIYAMA Jiro Fukui Medical University.Umversity HoSpital,Professsor, 医学部・附属病院, 助手 (40283171)
MUTO Tatsuro Fukui Medical University,Medical Department,Lectiire, 医学部・附属病院, 講師 (60190857)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Amyloid β protein / apppoposis / PC12 / Tyrosine Kinase / Trk / phosphorylation / リン酸化反応 |
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| Research Abstract |
1) The neurotoxicity of amyloid β protein (a-β) : The fibrfflar form of a-β induced the tyrosine autophosphorylation of the Trk protein in PC12 cells. The reaction peaked at 10 mins and returned at 60 mins. The MAPK and Akt kinase in the downstream of Trk were also transiently activated. These reactions seemed to be a protective reaction.
2) The effect of PS1 mutation to the intraceUar signal transduction through Trk. : The Trk phosphorylation by NGF was markedly decreased in the neuroblastoma cell line overexpressed mutated-PSl or wild type-PS l. EspeciaUy in the cells overexressed mutated-PSl, the immunoreactivity to Trk protein could not be found on the cell membrane, but in the cytosol, by a confocal microscopy, showing that the post translational modification or intracellar translocation of the Trk protein was disturbed in the cells. The experiments using ganglioside GMl-defective cells (NG-CR72 cells) showed that gangliosides had an important function for the localization of Trk protein.
3) The effect of HMG-CoA reductase inhibitor (statin) to the aggregation of a-β : The aggregation or elongation of a-β was examined by the method using fluorescent dye, tioflavine T. All statins except simvastatin inhibited the aggregation of a-β. As this inhibition could be found at very high concentration of statins, it was not thought that the dose of statins clinically used can block the formation of amyloid plaque in the brain.
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Research Products
(13 results)
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[Publications] Mutoh, T.,Sobue, G., Hamano, T., Kuriyama, M., Hirayama, M., Yamamoto, M., Mitsuma, T.: "Decreased phosphorylation levels of TrkB neurotrophin receptor in the spinal cords from patients with amyotrophic lateral sclerosis."Neurochem Res. 25. 239-245 (2000)
Description
「研究成果報告書概要(欧文)」より
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