Erythropoietin(Epo)ismostcommonlyknownasthecytokinesecretedbythekidneysthatstimulatesredbloodcellproductionandisusedasadrugforthetreatmentofanemias.Epoisalsosecretedinthebraininresponsetohypoxia,suchasischemicstroke.Epoproductioninthebrainisstimulatedbythehypoxia-inducIBLetranscriptionfactorHIF-1(seeHIFpathway).AdmiNISTrationofEpotothebraininrodentsbeforehypoxicstressorotherneuronalstressesisneuroprotective,preventingneuronalapoptosis.Theerythropoietinreceptor(EpoR)isknowntoassociatewithJAKkinasesthatphosphorylateandactivatetheSTATfamilyoftranscriptionfactors(SeeEpopathway).TheneuroprotectionbyEpoinvolvescross-talkbetweenEporeceptorandanti-apoptoticpathwaysthroughactivationofNF-kBbytheJAK2kinase(seeNF-kBpathway).EpostimulatesJAK2phosphorylationofI-kB,releasingNF-kBtotranslocateintothenucleusandactivatetranscriptionofneuroprotectivegenes.NeuroprotectivegenesactivatedbyNF-kBincludetheanti-oxidantenzymemanganesesuperoxidedismutaseandcalbindin-D(28k).Theerythropoietinreceptorisalsoessentialforproperbraindevelopmentinmice.TheabsenceofEpoRcauseshighlevelsofneuronalapoptosisinthedevelopingmousebrain,furtherconfirmingtheimportantroleofEpoasaneuroprotectiveagent.

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