title: A new agonist of the erythropoietin receptor, Epobis, induces neurite outgrowth and promotes neuronal survival.
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:EPOR(2) 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.
authors.affiliation: Protein Laboratory, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. stasya@sund.ku.dk
authors.forename: Stanislava
authors.initials: S
authors.lastname: Pankratova
authors.forename: Bing
authors.initials: B
authors.lastname: Gu
authors.forename: Darya
authors.initials: D
authors.lastname: Kiryushko
authors.forename: Irina
authors.initials: I
authors.lastname: Korshunova
authors.forename: Lene B
authors.initials: LB
authors.lastname: Køhler
authors.forename: Mette
authors.initials: M
authors.lastname: Rathje
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bock
authors.forename: Vladimir
authors.initials: V
authors.lastname: Berezin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004921:Erythropoietin / Q000737:chemistry / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008958:Models, Molecular; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D051381:Rats; D017208:Rats, Wistar; D017467:Receptors, Erythropoietin / Q000819:agonists* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020349:Surface Plasmon Resonance; D014162:Transfection
chemical_list: D018696:Neuroprotective Agents; D010455:Peptides; D017467:Receptors, Erythropoietin; D004921:Erythropoietin