FerroptosisandItsRoleinDiverseBrainDiseasesAbigailWeiland1&YameiWang2&WeihuaWu2&XiLan1&XiaoningHan1&QianLi2,3&JianWang1Received:9August2018/Accepted:18October2018#SpringerScience+BusinessMedia,LLC,partofSpringerNature2018AbstractFerroptosisisarecentlyidentified,iron-regulated,non-apoptoticformofcelldeath.Itischaracterizedbycellularaccumulationoflipidreactiveoxygenspeciesthatultimatelyleadstooxidativestressandcelldeath.Althoughfirstidentifiedincancercells,ferroptosishasbeenshowntohavesignificantimplicationsinseveralneurologicdiseases,suchasischemicandhemorrhagicstroke,Alzheimer’sdisease,andParkinson’sdisease.Thisreviewsummarizescurrentresearchonferroptosis,itsunderlyingmechanisms,anditsroleintheprogressionofdifferentneurologicdiseases.Understandingtheroleofferroptosiscouldprovidevaluableinformationregardingtreatmentandpreventionofthesedevastatingdiseases.KeywordsFerroptosis.Braindisease.Stroke.CancerIntroductionFerroptosis,firstdescribedbyDixonetal.in2012,isaformofcelldeathcharacterizedbyaccumulationofintracellulariron[1].Itisdefinedbydepletionofplasmamembraneunsaturatedfattyacidsandaccumulationofiron-inducedlipidreactiveoxygenspecies(ROS)[2].Theover-accumulationoflipidROSleadstoanoxidativestressresponseincellsthatcauseslethaldamagetoproteins,nucleicacids,andlipids[3]andeventuallytocelldeath.Thus,ferroptosisrequiresthecoinci-dentdepletionofglutathione(GSH)orinactivationofglutathione-dependentantioxidantenzymeglutathioneperox-idase4(GPX4)andtheincorporationofoxidizablepolyun-saturatedfattyacidsintophospholipids[4].Ferroptosisdiffersfromapoptosis,necrosis,andautophagymorphologically,biochemically,andgenetically[1].Underelectronmicroscopy,ferroptoticcellsexhibitshrunkenmito-chondria,whereasmitochondriaareusuallyswolleninotherformsofcelldeath[1].Initially,Dixonetal.identifiedadis-tinctsetofgenesthatregulatetheferroptoticmechanism,in-cludingribosomalproteinL8(RPL8),ironresponseelementbindingprotein2(IREB2),andATPsynthaseF0complexsubunitC3(ATP5G3)[1].Laterstudiesshowe...
