[Molecular mechanisms of brain peptide-containing drugs: cortexin]

The goal of treatment of brain pathologies may be regarded as re-establishment of optimal brain plasticity. Disturbances in neuroplasticity are associated with the appearance of multiple targets that should be subjects for pharmacological correction. Peptide hydrolysates derived from animal brain became a basis for multi-component organ-specific drugs which are widely used for treatment of cerebral pathologies. Potentially, the presence of many components in such drugs may be beneficial for simultaneous effects on different targets. In this article, new data are analyzed related to relevant molecular mechanisms underlying neuroprotective properties of cortexin. On a model of accelerated aging in rats, cortexin restored the ratio of pro- and antioxidative systems and demonstrated a significant anti-inflammatory effect both in the brain and at the systemic level. In in vitro experiments cortexin effectively and tissue-specifically inhibited brain caspase-8. Neuron-specific proteins β5-tubulin, creatine kinase B and protein 14-3-3 α/β were shown to be molecular partners of cortexin peptides in the brain. Thus, potential molecular mechanisms of cortexin neuroprotective effects are various and associated with key processes underlying neuroplasticity: signal transduction, energy metabolism, proteolytic protein modification, cell structure, as well as neuroinflammation. The pleiotropicity of mechanisms of cortexin action is based on the composition of the drug containing a variety of neuropeptides. The tissue specificity of these mechanisms determines to a significant degree the efficacy of the drug in treatment of cerebral pathologies.