Neuroprotective effect of Cu,Zn-superoxide dismutase fused to a TCTP-derived protein transduction domain.

Previously, we have reported that a 10-amino acid peptide (MIIYRDLISH) derived from the NH(2)-terminus of the human translationally controlled tumor protein (TCTP) functions as a protein transduction domain (PTD). In this study, we evaluated the transduction ability of SOD fused to TCTP-PTD (TCTP-SOD) into various cell lines. We also evaluated its ability to protect cells against paraquat-induced cell damage, in vitro and its neuroprotective effect in vivo against kainic acid-induced neuronal damage in an animal model. TCTP-SOD was transduced into various cell lines in a dose- and time-dependent manner without cytotoxic effect. Furthermore, TCTP-SOD showed cytoprotective activity in SH-SY5Y cells, and intraperitoneally, injected TCTP-SOD was delivered into the mouse brain and protected the cells in the hippocampal region against the damage induced by kainic acid. We propose TCTP-SOD as a potential candidate drug for treatment of brain diseases.