2010 Fiscal Year Final Research Report
Pathological study for a protein anchoring tau kinases and tau phosphatases in Alzheimer brain tissues
| Project/Area Number |
20591024
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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 | Kobe University |
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Principal Investigator |
KAWAMATA Toshio Kobe University, 大学院・保健学研究科, 教授 (70214690)
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| Co-Investigator(Renkei-kenkyūsha) |
ONO Yoshitaka 神戸大学, バイオシグナル研究センター, 教授 (10243297)
MUKAI Hideyuki 神戸大学, バイオシグナル研究センター, 准教授 (80252758)
TAKAHASHI Mikiko 帝京平成大学, 薬学部, 教授 (90324938)
MAEDA Kiyoshi 神戸学院大学, 総合リハビリテーション学部, 教授 (80116251)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 痴呆 / シグナル伝達 / 神経科学 / 脳神経疾患 |
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| Research Abstract |
We investigated possible roles of abnormal intracellular signaling in the tau pathology in Alzheimer's disease (AD) for FKBP12 and the phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a peptidyl-prolyl cis-trans isomerase known to be important in protein assembly, folding and transportation and a tumor-suppressor respectively by using Western blotting and microscopic analyses in postmortem brain tissues from elderly controls and the patients with AD. FKBP12-positive or PTEN-positive granules were located in the nucleus, the cytoplasm of cell bodies and the proximal portion of dendrites and axons in control brains. Reduced expression of FKBP12 or PTEN was seen in the remaining neurons, especially in the tangle-bearing neurons in AD. In addition, these molecules were redistributed in damaged neurons from the nucleus to the cytoplasm or to the neuritic pathology such as neuropil threads, degenerative neurites and intracellular tangles. Labeling of some reactive astrocytes around senile plaques was seen for FKBP12 or PTEN. Double labeling of tangles was observed either for PTEN and GSK3β or for PTEN and MEK. Thus, our results suggest that FKBP12 or PTEN delocalized from the nucleus to the cytoplasm and to the tangles may cause a deregulation of PI3K pathway in the cytoplasm and may induce the nuclear dysfunction in AD neurons.
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[Journal Article] A peptidyl-prolyl isomerase, FKBP12, accumulates in Alzheimer neurofibrillary tangles.2009
Author(s)
Sugata H, Matsuo K, Nakagawa T, Takahashi M, Mukai H, Ono Y, Maeda K, Akiyama H, Kawamata T.
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Journal Title
Neuroscience Letters 459
Pages: 96-99
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[Remarks] ホームページ等
