简介：MolecularmechanismsoftheKru?ppel-likefamilyoftranscriptionfactors(KLFs)havebeenstudiedmoreinproliferatingcellsthaninpost-mitoticcellssuchasneurons.WerecentlyfoundthatKLFsregulateintrinsicaxongrowthabilityincentralnervoussystem(CNS)neuronsincludingretinalganglioncells,andhippocampalandcorticalneurons.Withatleast15of17KLFfamilymembersexpressedinneuronsandatleast5structurallyuniquesubfamilies,itisimportanttodeterminehowthiscomplexfamilyfunctionsinneuronstoregulatetheintricategeneticprogramsofaxongrowthandregeneration.BycharacterizingthemolecularmechanismsoftheKLFfamilyinthenervoussystem,includingbindingpartnersandgenetargets,andcomparingthemtodefinedmechanismsdefinedoutsidethenervoussystem,wemaybetterunderstandhowKLFsregulateneuritegrowthandaxonregeneration.

简介：Themainpathophysiologyofcerebralischemiaisthestructuralalterationintheneurovascularunit,coincidingwithneurovascularmatrixdegradation.Resveratrolhasbeenreportedtobeoneofthemostpotentchemopreventiveagentsthatcaninhibitcellularprocessesassociatedwithischemicstroke.Matrixmetalloproteinases(MMPs)hasbeenconsideredasapotentialdrugtargetforthetreatmentofcerebralischemia.Toexplorethis,wetriedtoinvestigatetheinteractionofresveratrolwithMMPsthroughmoleculardockingstudies.At30minutesbeforeand2hoursaftercerebralischemia/reperfusioninducedbyocclusionofthemiddlecerebralartery,40mg/kgresveratrolwasintraperitoneallyadministered.Afterresveratroladministration,neurologicalfunctionandbrainedemaweresignificantlyalleviated,cerebralinfarctvolumewassignificantlyreduced,andnitriteandmalondialdehydelevelsinthecorticalandstriatalregionsweresignificantlydecreased.ThemoleculardockingstudyofresveratrolandMMPsrevealedthatresveratroloccupiedtheactivesiteofMMP-2andMMP-9.Thebindingenergyofthecomplexeswas–37.848672kJ/moland–36.6345kJ/molforMMP-2andMMP-9,respectively.IncaseofMMP-2,Leu164,Ala165andThr227wereengagedinH-BondingwithresveratrolandincaseofMMP-9,H-bondingwasfoundwithGlu402,Ala417andArg424residues.ThesefindingscollectivelyrevealthatresveratrolexhibitsneuroprotectiveeffectsoncerebralischemiathroughinhibitingMMP-2andMMP-9activity.