TAT-GluR6-9c is a peptide derived from the nine C terminal residues of the kainate receptor subunit GluR6, linked to the cell penetrating sequence TAT. TAT-GluR6-9c is able to perturb the interaction of GluR6 with postsynaptic density protein 95 (PSD-95) and suppress the assembly of the GluR6-PSD-95-mixed lineage protein kinase 3 (MLK3) signalling module, causing inhibition of c-Jun N-terminal kinase (JNK) activation. JNK has an important role during global and focal cerebral ischemia/reperfusion and consistent with JNK inhibition, TAT-GluR6-9c pretreatment decreases neuronal death induced by kainate in vitro. In vivo, TAT-GluR6-9c protects against kainate-induced epileptic seizure and has a neuroprotective effect against ischaemic brain damage, significantly decreasing neuronal degeneration.
