2006 Fiscal Year Final Research Report Summary
Analysis of functional roles of presenilin and GSK-3β in molecular mechanism of neurofibrillary tangles
| Project/Area Number |
17590860
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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 | Gunma University |
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Principal Investigator |
IKEDA Masaki Gunma University, Neurology, Assistant Professor, 大学院・医学系研究科, 助手 (50222899)
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| Project Period (FY) |
2005 – 2006
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| Keywords | tauopathy / Dementia / Alzheimer's disease / FTDP-17 / neurofibrillary tangle |
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| Research Abstract |
Glycogen synthase kinase-3β(GSK-3β) plays an important role in phosphorylation of tau. This evidence is thought to be induced to form neurofibrillary tangles (NFT) observed in tauopathies including Alzheimer's disease. It is crucial to elucidate the mechanism of GSK-3β involved in NFT and neuronal cell death, to develop novel therapy for these diseases. To elucidate immunocytochemical changes of cytoskeltal structures in GSK-3β transgenic mice. To examine immunocytochemical study and Western blot of GSK-3β transgenic mice brains at 3, 8 and 12 months. We examined immunocytochemical study of transgenic mice overexpressing a constitutively active GSK-3β(S9A), and demonstrate that the expression of GSK-3β increased in the cytoplasm and dendrites of neuronal cells in age dependent manner at 3 to 12 months. The reduction of the level of the microtubule-associated protein 2 (MAP2) in brain and in spinal cord, and immunoreactivity of neurofilament by antibodies SMI-31, NF-200 slightly decreased in the dendrites of neurons. These findings suggested that overexpression of GSK-3β in vivo led to decrease of phophorylated neurofilaments and MAP2 protein in neuronal cells, leading to aberrant change of cytoskeltal structures and neuronal dysfunction.
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Research Products
(13 results)
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[Journal Article] Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice.2005
Author(s)
Ikeda M, Shoji M, Kawarai T, Kawarabayashi T, Matsubara E, Murakami t, Sasaki A, Tomidokoro Y, Ikarashi Y, Kuribara H, Ishiguro K, Hasegawa M, Yen SH, Chishti MA, Harigaya Y, Abe K, Okamoto K, St George-Hyslop P, Westaway D.
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Journal Title
American Journal of Pathology 166(2)
Pages: 521-531
Description
「研究成果報告書概要(欧文)」より
