2013 Fiscal Year Final Research Report
Analysis of the neurotoxicity which is induced by the intracellular domain of APP
| Project/Area Number |
23500442
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Keywords | アルツハイマー病 / γーセクレターゼ / APP / 細胞内ドメイン / 認知症 / 神経変性疾患 / シグナル伝達 / アポトーシス |
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| Research Abstract |
It has shown that the intracellular domain of APP (AICD) is released from the cell membrane into the cytoplasm by gamma-secretase and translocates to the nucleus. We have also shown that AICD markedly altered gene expression in the nucleus, and induced neuron specific apoptosis.
In this study, we identified a large number of transcription factors which bound to AICD. These results suggest the reason why AICD can control expressions of many genes. From the point of view of apoptosis, E2F1 will be focused. In addition, we partially purified the AICD-phosphatase which may control translocation of AICD to the nucleus. We will identify this enzyme by a mass spectrum. Furthermore, we tried to make the transgenic mice which specifically express AICD in brain. Unfortunately, these mice were embryonic lethal that may be caused by strong neurotoxicity of AICD. To evade embryonic lethal, we will try to make mice, which express AICD only in less than half of brain neurons using Brainbow strategy.
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