Pathogenic substantiation of application of erythropoietin modified forms and peptide analogues as cytotprotectors

Abstract

Provides a review of the evidence from experimental and clinical studies on the blood-forming and non-blood-forming tissue protective effects of erythropoietin. Information on its side effects (stimulation of tumor growth, autoimmune reactions, arterial hypertension, etc.), limiting the clinical use as a cytoprotector, is summarized. Well-known modifications of the erythropoietin molecule with a tissue protective effect are considered, in particular, desialylated (asialoEPO), carboxylated (CEPO) and glutaraldehyde (GEPO) cytokine analogues. The results of biomedical studies describing the tissue protective effects of these compounds, as well as possible mechanisms of their receptor action, are presented. The article discusses the main short-chain erythropoietin mimetics that reproduce individual active regions of cytokine amino acid sequence and contain from 11 to 25 amino acids: Helix B, ARA290, Eportis, Epopeptide-ab, MK-X, Epobis, NL100. The biochemical mechanisms of cytoprotective action of erythropoietin and its derivatives are considered, including binding to the heterodimeric receptor of non-blood-forming tissues and activation of intracellular signaling molecules possessing properties of apopotosis inhibitors. It was noted that the tissue protective effect of erythropoietin in vivo is observed in hemostimulating doses and is accompanied by side effects. At the same time, the use of modified forms of erythropoietin and its short-chain peptide analogues, which have a high affinity for the isoform of the erythropoietin receptor of non-blood-forming tissues and do not have hematopoietic properties, allows avoiding the development of side effects and reducing effective doses by 10-20 times.