2006 Fiscal Year Final Research Report Summary
Regulation and Analysis of Excitatory Neuronal Cell Death by Protein Transduction Therapy
| Project/Area Number |
17500212
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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 |
Neuroscience in general
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| Research Institution | Mitsubishi Kagaku Institute of Life Sciences |
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Principal Investigator |
MATSUSHITA Masayuki Mitsubishi Kagaku Institute of Life Sciences, Brain Stroke Resarch Group, Principal Investigator, 研究部門・脳梗塞研究グループ, 主任研究員 (30273965)
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| Co-Investigator(Kenkyū-buntansha) |
SAITOH Ken Mitsubishi Kagaku Institute of Life Sciences, Brain Stroke Research Group, Postdoctoral Researcher, 研究部門・脳梗塞研究グループ, 特別研究員 (70426584)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Protein transduction system / PTD / Calpain / TRPM7 / Neuron / Apoptosis / Ischemia / NMDA |
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| Research Abstract |
With the elucidation of the human genome, exhaustive analysis of genomic data related to gene transcription and the structure and function of translated protein products has progressed rapidly. Delivery of proteins and their functional domains or inhibitory peptides directly into the neuron is ideal to treat excitatory neuronal cell death and related signal transduction s.
However, the protein is often entrapped inside macropinosomes in the cytoplasm. Therefore, high dose concentrations of the protein are needed for it to function effectively. To overcome this problem, in this project, polyarginine was linked with the NH(2)-terminal domain of influenza virus hemagglutinin-2 subunit (HA2), which is a pH-dependent fusogenic peptide that induces the lysis of membranes at low pH levels. We also designed the calpain and TRPM7 inhibitory peptide fused with protein transduction domain and examined the protective effect for ischemic neuronal cell death. These designed peptides were significantly protected against ischemic cell death. These data clearly show that protein transduction system is useful method for treat ischemic neuronal cell death.
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