ReviewFerroptosisInhibition:Mechanismsand[280_TD$DIF]OpportunitiesJosePedroFriedmannAngeli,1,*RonShah,2DerekA.Pratt,2,*[281_TD$DIF]andMarcusConrad1,*Thepastdecadehasyieldedtremendousinsightsintohowcellsdie.Thishascome[283_TD$DIF]withourunderstandingthatseveraldistinctformsofcelldeathareencompassedundertheumbrellatermnecrosis.Amongthesedistinctformsofregulatednecroticcelldeath,ferroptosishasattractedconsiderableatten-tionowingtoitsputativeinvolvementindiversepathophysiologicalprocesses.Akeyfeatureoftheferroptosisprocessistherequirementofphospholipidperoxidation,aprocessthathasbeen[284_TD$DIF]linkedwithseveralhumanpathologies.Nowwith[285_TD$DIF]theestablishmentofaconnectionbetweenlipidperoxidationandadistinctivecelldeathpathway,thesearchfornewsmallmoleculesabletosuppresslipidperoxidationhasgainedmomentumandmayyieldnovelcyto-protectivestrategies.Wereviewhereadvancesinourunderstandingoftheferroptoticprocessandsummarizethedevelopmentoflipidperoxidationinhibitorswiththeultimategoalofsuppressingferroptosis-relevantcelldeathandrelatedpathologies.FerroptosisUnderstandinghowcellsdiepresentsanintrinsicandenormoustranslationalpotentialbecauseitoffersuniqueopportunitiestointerferewithprocessesassociatedwithcelldeathandsurvival.Approachesattemptingtohaltcelldeathhavebeenstronglybiasedtowardsthestudyofapoptosisbecausethishaslongbeenconsideredtobetheonlyformofcelldeaththatisamenabletopharmacologicalandgeneticintervention.However,duringthepastdecadeseverallandmarkstudieshaveidentifiedadditionalregulatorymechanismsandsignalingpathwaysthatgovernpreviouslyunrecognizednecroticcelldeathroutines[1].Amongthesenovelregulatedformsofnecrosis,ferroptosishasattractedconsiderableattentionowingtoitsimplicationinseveralpathophysiologicalcontextssuchastumorsuppression[2,3],antiviralimmunity[4],neurodegeneration[5],andischemia/reperfusioninjury(IRI)[6].Basedonmor-phological,biochemical,andgeneticcriteria,ferroptosiswasshowntobedistinctfromotherdescribedcelldeathmodalities[7].Morphologicalchangesd...
