6533b7defe1ef96bd1276675

RESEARCH PRODUCT

Derivatives of Erythropoietin That Are Tissue Protective But Not Erythropoietic

Thomas N. SagerAlessandra SfacteriaAlessandra SfacteriaMarina BianchiMarcel LeistLars TorupSøren ChristensenSerhat ErbayraktarSerhat ErbayraktarJacob NielsenMichael BrinesLars ØStergaard PedersenPekka KallunkiThomas ColemanOsman YilmazOsman YilmazGiovanni GrassoGiovanni GrassoLone HelboeZübeyde ErbayraktarZübeyde ErbayraktarPietro GhezziPia VillaNecati GokmenQiao-wen XieRoberto BianchiMaddalena FratelliCarla Cerami-handCostanza SavinoJens GerwienAnthony CeramiMette NielsenAnna Kirstine Larsen

subject

Encephalomyelitis Autoimmune ExperimentalEncephalomyelitiscarbamylated erythropoietinApoptosisPharmacologyLigandsNeuroprotectionRats Sprague-DawleyMiceStructure-Activity RelationshipDiabetic Neuropathiesddc:570hemic and lymphatic diseasesReceptors ErythropoietinmedicineAnimalsHumansErythropoiesisReceptorErythropoietinCells CulturedNeuronsMice Inbred C3HBinding SitesMultidisciplinaryChemistryExperimental autoimmune encephalomyelitisErythropoietin; erythropoietin receptor; carbamylated erythropoietin; neuroprotective agentsmedicine.diseaseRecombinant ProteinsRatsErythropoietin receptorStrokeNeuroprotective AgentsErythropoietin Erythropoietin derivative NeuroprotectionHematocritMutagenesisErythropoietinDrug DesignImmunologyErythropoiesisFemaleNervous System DiseasesSignal transductionerythropoietin receptorSpinal Cord CompressionSignal Transductionmedicine.drug

description

Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype–selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.

yearjournalcountryeditionlanguage
2004-07-09Science
https://doi.org/10.1126/science.1098313