Tat-NTS peptide is a cell-penetrating peptide consisting of Tat fused to amino acid residues R228 to F237 of the repeat III domain of ANXA1, which functions as a unique nuclear translocation signal (NTS). Tat-NTS peptide specifically blocks the interaction of ANXA1 with importin beta and consequently the nuclear translocation of ANXA1. Tat-NTS peptide inhibits the transcriptional activity of p53, decreases Bid expression, suppresses activation of the caspase-3 apoptosis pathway and improves survival of neurons subjected to oxygen-glucose deprivation in vitro. In a focal brain ischemia animal model, Tat-NTS peptide reduces neuronal apoptosis in the ischemic zone and effects a dramatic reduction of infarct volume and a parallel improvement in neurological function after reperfusion.
