Prothymosin ? as robustness molecule against ischemic stress to brain and retina
Following stroke or traumatic damage, neuronal death via both necrosis and apoptosis causes loss of functions, including memory, sensory perception, and motor skills. As necrosis has the nature to expand, while apoptosis stops the cell death cascade in the brain, necrosis is considered to be a promising target for rapid treatment for stroke. We identified the nuclear protein, prothymosin alpha (ProT?) from the conditioned medium of serum-free culture of cortical neurons as a key protein-inhibiting necrosis. In the culture of cortical neurons in the serum-free condition without any supplements, ProT? inhibited the necrosis, but caused apoptosis. In the ischemic brain or retina, ProT? showed a potent inhibition of both necrosis and apoptosis. By use of anti-brain-derived neurotrophic factor or anti-erythropoietin IgG, we found that ProT? inhibits necrosis, but causes apoptosis, which is in turn inhibited by ProT?-induced neurotrophins under the condition of ischemia. From the experiment using anti-ProT? IgG or antisense oligonucleotide for ProT?, it was revealed that ProT? has a pathophysiological role in protecting neurons in stroke.
robustness necrosis apoptosis ischemia brain-derived neurotrophic factor cell death mode switch