Regulation and Analysis of Excitatory Neuronal Cell Death by Protein Transduction Therapy

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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.