Peptide Derivatives of Erythropoietin in the Treatment of Neuroinflammation and Neurodegeneration.

During the past 35 years, recombinant DNA technology has allowed the production of a wide range of hematopoietic and neurotrophic growth factors including erythropoietin (EPO). These have emerged as promising protein drugs in various human diseases. Accumulated evidences have recently demonstrated the neuroprotective effect of EPO in preclinical models of acute and chronic degenerative disorders. Nevertheless, tissue protective effect of EPO could not be translated to the clinical trials because of common lethal thromboembolic events, erythropoiesis and hypertension. Although chemically modified nonerythropoietic analogs of EPO bypass these side effects, high expense, development of antidrug antibodies, and promotion of tumorigenicity are still concern especially in long-term use. As an alternative, nonerythropoietic EPO mimetic peptides can be used as candidate drugs with their high potency and selectivity, easy production, low cost, and immunogenicity properties. Recent experimental studies suggest that these peptides prevent ischemic brain injury and neuroinflammation. The results of clinical trial in patients with neuropathic pain are also promising. Herein, we summarize these studies and review advanced experimental and in silico methods in peptide drug discovery.