A new agonist of the erythropoietin receptor, Epobis, induces neurite outgrowth and promotes neuronal survival

作者：Pankratova Stanislava^*; Gu Bing; Kiryushko Darya; Korshunova Irina; Kohler Lene B; Rathje Mette; Bock Elisabeth; Berezin Vladimir

来源：Journal of Neurochemistry, 2012, 121(6): 915-923.

DOI：10.1111/j.1471-4159.2012.07751.x

• erythropoietin
• neurite outgrowth
• neuronal survival
• peptide agonist

J. Neurochem. (2012) 121, 915923. Abstract Apart from its hematopoietic activity, erythropoietin (EPO) is also known as a tissue-protective cytokine. In the brain, EPO and its receptor are up-regulated in response to insult and exert pro-survival effects. EPO binds to its receptor (EPOR) via high- and low-affinity binding sites (Sites 1 and 2, respectively), inducing conformational changes in the receptor, followed by the activation of downstream signaling cascades. Based on the crystal structure of the EPO:EPOR2 complex, we designed a peptide, termed Epobis, whose sequence encompassed amino acids from binding Site 1. The present study shows that the Epobis peptide specifically binds to EPOR and induces neurite outgrowth from primary neurons in an EPOR-expression dependent manner. Furthermore, Epobis promoted the survival of hippocampal and cerebellar neuronal cultures after kainate treatment and KCl deprivation, respectively. Thus, we identified a new functional agonist of EPOR with the potential to promote neuroregeneration and neuroprotection.

• 出版日期2012-6