Prothymosin α-derived hexapeptide prevents the brain damage and sequelae due to ischemia-hemorrhage

ProTα discovered as a necrosis-inhibitor from the conditioned medium of cortical culture also shows a potent survival action in brain and retinal ischemia/reperfusion models. The proposed mechanisms are the initial cell death mode switch from necrosis to apoptosis, which is subsequently inhibited by neurotrophic factors in vivo. It should be noted that ProTα and its derived hexapeptide P6Q completely suppress the cerebral hemorrhage induced by late tPA treatment (4.5 h) after the brain ischemia/reperfusion. Mechanisms underlying their beneficial actions may be related to the fact that ProTα inhibits the production of matrix metalloproteases (MMPs) in microglia and vascular endothelial cells. However, as P6Q inhibits MMPs in vascular endothelial cells, but not in microglia, the suppression of MMP production in endothelial cells seems to play major roles in the late tPA-induced hemorrhage. Although the tPA-treatments could enable the survival of patients with stroke, the post-stroke sequelae are the next clinical issues to be solved. The use of small peptide P6Q revealed the blockade of post-stroke pain, depression and memory-learning deficits in animal models. Furthermore, recent studies also showed that P6Q supplementation increased the viability of human induced pluripotent stem (iPS) cell-derived retinal pigment epithelium cell suspensions during the storage and P6Q attenuated the cisplatin-induced acute kidney injury.