ReviewRegulationandRolesofAutophagyatSynapsesVassilikiNikoletopoulou1andNektariosTavernarakis1,2,*Geneticstudieshavedemonstratedthatconditionalablationofcoreautoph-agygenesintheneurallineageleadstoprogressiveneurodegeneration,indicatingthatthiscatabolicpathwayisindispensableforneuronalmainte-nance.However,accumulatingevidencealsoindicatesthatautophagyisnotmerelyahousekeepingprocess.Instead,autophagymaybedynamicallyregulatedindifferentneuronalcompartmentsanddictatetheturnoverofselectedcargoinatime-andspace-dependentmannerandthuscontributetospecializedneuronalfunctions.Here,wereviewthemechanismsregulatingautophagyinneuronsanddiscussrecentfindingsontheroleofautophagyinsynapticmorphologyandfunction.Moreover,wediscussrelevantquestionsthatremainopenandhighlightforthcomingissuesinthefieldofneuronalautophagy.NeuronalAutophagy:NewViewsAutophagyisacatabolicprocessthatdegradesmacromoleculesandorganellesbydeliveringthemtothelysosome.Threemechanisticallydistincttypes,microautophagy,chaperone-mediatedautophagy,andmacroautophagy,havebeendescribed[1,2].Unlikethefirsttwotypes,macroautophagyisamultistepprocessthatentailstheformationofadouble-membranevesicle,theautophagosome.Themechanismsofmacroautophagyhavebeenreviewed[3].Briefly,autophagosomebiogenesisstartswiththeassemblyofapre-autophagosomalstruc-ture(PAS),whichisnecessaryforthenucleation(seeGlossary)ofaphagophore.Thephagophoreisadouble-membranestructurethatsequestersautophagiccargoasitelongatesandclosestoformtheautophagosome.Here,wewillfocusonmacroautophagy,whichwillbereferredtohereafterasautophagy.Autophagywasregardedasahousekeepingprocessthatensuredtheclearanceofunwantedmaterialsandpreventedtheiraggregationinordertosafeguardcellularfunction.Earlyworkinvestigatingtheroleofautophagyinthebrainindicatedthatconditionalablationinthenervoussystemofcoreautophagygenes,suchasatg5oratg7,ledtotheaccumulationofaggregatesofubiquitinatedproteinsinneuronsandlateonsetneurodegeneration[4,5].However,recentworksuggeststhatinadditiontocellularma...
