| Project/Area Number |
18500263
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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 | Kyoto University |
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Principal Investigator |
KINOSHITA Ayae Kyoto University, Graduate School of Medicine, Assistant Professor (80321610)
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| Co-Investigator(Kenkyū-buntansha) |
UEMURA Kengo Kyoto University, Graduate School of Medicine, Assistant Professor (00378663)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Alzheimer's disease / presenilin / synapse / phosphorylation / signal transduction / cadherin / catenin / シナプス可塑性 / N-cadherin |
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| Research Abstract |
In order to investigate the mechanism of synaptic dissociation which underlies the synaptic plasticity, we focused on the functions of neuronal adhesion molecules, N-cadherin. N-cadherin is an adhesion molecule, which adheres synaptic clefts in the brain. These adhesion molecules are recently reported to cleaved by several secretases, such as gamma-secretase. After the cleavage in the membranous portion, its cytoplasmic fragment is released into the cytoplasm and enters the nucleus, then plays a role as a modulator of the transactivation. This process is called "Regulated intramembrane proteolysis (RIP)". By using the mouse primary neurons we confirmed that N-cadherin was actually cleaved by some stimuli, and the translocation of its cytoplasmic fragment upregulation of beta-catenin which is an essential molecule for neuronal growth and differentiation. We speculated that this process is also important in vivo, so to confirm in vivo relevancy, we started to generate mutant PS1 (gamma-secretase)-knock-in mouse in which N-cadherin is not cleaved by gamma-secretase. We have already got the F1 hetero mouse. We hope this study will reveal a new insight into synaptic dissociation caused by secretase-mediated cleavages. We would like to deepen this result and hope to elucidate the underlying mechanism of synaptic plasticity. Since gamma-secretase is one of the important targets for the treatment of Alzheimer's disease, our research may help us understand the pathological mechanism of Alzheimer's disease.
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