2007 Fiscal Year Final Research Report Summary
Investigation of the synaptic dissociation mechanism
| 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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| Keywords | Alzheimer's disease / presenilin / synapse / phosphorylation / signal transduction / cadherin / catenin |
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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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Research Products
(23 results)
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[Journal Article] Amyloid beta inhibits ectodomain shedding of N-cadherin via down-regulation of cell-surface NMDA receptor.2007
Author(s)
Uemura, K., Kuzuya, A., Aoyagi, N., Ando, K., Shimozono, Y., Ninomiya, H., Shimohama, S., & Kinoshita, A.
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Journal Title
Neuroscience 145
Pages: 5-10
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] GSK3beta activity modifies the localization and function of presenilin12007
Author(s)
Uemura, K., Kuzuya, A., Shimozono, Y., Aoyagi, N., Ando, K., Shimohama, S., Kinoshita, A
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Journal Title
Journal of Biological Chemistry 282
Pages: 15823-32
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Amyloid beta inhibits ectodomain shedding of N-cadherin via down-regulation of cell-surface NMDA receptor2007
Author(s)
Uemura, K., Kuzuya, A., Aoyagi, N., Ando, K., Shimozono, Y., Ninomiya, H., Shimohama, S., Kinoshita, A
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Journal Title
Neuroscience 145
Pages: 5-10
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Activity-dependent regulation of beta-catenin via epsilon-cleavage of N-cadherin2006
Author(s)
Uemura, K., Kihara, T., Kuzuya, A., Okawa, K., Nishimoto, T., Bito, H., Ninomiya, H., Sugimoto, H., Kinoshita, A., Shimohama, S
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Journal Title
Biochem Biophys Res Commun 345
Pages: 951-958
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Characterization of sequential N-cadherin cleavage by ADAMIO. and PS12006
Author(s)
Uemura, K., Kihara, T., Kuzuya, A., Okawa, K., Nishimoto, T., Bito, H., Ninomiya, H., Sugimoto, H., Kinoshita, A., Shimohama, S
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Journal Title
Neurosci Lett 402
Pages: 278-283
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 介護における殺人の傾向2007
Author(s)
日吉和子、カール・ベッカー、木下彩栄
Organizer
第11回日本健康福祉政策学会
Place of Presentation
岡山
Year and Date
2007-12-08
Description
「研究成果報告書概要(和文)」より
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[Presentation] Tne N-cadherin enhances extracelluar secretion of Abeta and modulates Ab40/42 ratio2007
Author(s)
Uemura, K., Aoyagi, N., Ando, K., Takahashi, R., Shimohama, S., Kinoshita, A
Organizer
26th Japan Society for Dementia
Place of Presentation
Osaka
Year and Date
2007-10-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The effect of amyloid beta protein on cadherin cleavage2007
Author(s)
Uemura, K., Aoyagi, N., Ando, K., Takahashi, R., Shimohama, S., Kinoshita, A
Organizer
48th Japan Society of Neurologica
Place of Presentation
Nagoya
Year and Date
2007-05-16
Description
「研究成果報告書概要(欧文)」より
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