STAT3 (signal transducer and activator of transcription protein 3) is a transcription factor, as well as an intracellular signal transducer, activated by cytokines, growth factors, and receptor-or nonreceptor-tyrosine kinases. Colivelin, which activates STAT3 signaling, is a neuroprotective humanin family peptide with potent long-term capacity against Aβ deposition, neuronal apoptosis, and synaptic plasticity deficits in neurodegenerative disease. In wild type C57BL/6 mice, colivelin (1mg/kg; intraperitoneal injection) resulted in improved motor and cognitive function with time, as well as reduced lesion volume suggesting that colivelin protects against ischemic brain injury, and improves neurological outcomes. In ischemic stroke mode, colivelin treatment significantly increased Bielschowsky sliver expressions in the ischemic brain, reduced TUNEL+ apoptotic cells and upregulated a bunch of anti-apoptotic genes, suggesting a beneficial effect of colivelin by attenuating neuronal death after brain ischemia. Moreover, STAT3 phosphorylation was elevated in colivelin group as compared to vehicle control, suggesting the activation of STAT3 induced by colivelin. Colivelin treatment mice exhibited enhanced axonal growth compared with vehicle, indicating that colivelin rescued neuronal damage after brain ischemia by improving axonal remodeling which might be associated with STAT3 activation[6].
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