简介：Strokeisaleadingcauseoflong-termdisability.Moststrokepatientsregaintheirfunctionpartiallyorfullyduringthefirst3–6monthsdependingonlocationandsizeofthelesion.Duringthisfunctionalrecoveryphase,corticalreorganizationorplasticityoccurs,andphysiologicalresponsivenessorneuronalexcitabilityisalteredintheipsilesionalandcontralesionalareas.However,howtodrivesuccessfulplasticchangesorsuccessfulstrokerecoveryarenotfullyelucidatedyet.

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简介：Demyelinationofthecentralnervoussystem(CNS)isahallmarkofmultiplesclerosis(MS),chronicinflammatoryandneurodegenerativedisease.Chronicdemyelinationfavorsneurodegenerationofdenudedaxons,whichisamajorcauseofirreversibleneuronaldeficitsanddisabilityinMSpatients(Lucchinettietal.,2000).MSremainsanincurabledisease,despiteformida-

简介：Accumulatingevidencefromepidemiologicalandexperimentalstudiesindicatethatobesity,anditsrelatedmetabolicconsequencesofinsulinresistanceandtype2diabetes,areassociatedwithacceleratedcognitivedecline(Yatesetal.,2012).Theetiologyofneurodegenerationinobesityisundoubtedlycomplex,withvascular,metabolic,inflammatory,andstructuralchangesalllikelytoplayarole(Yatesetal.,

简介：Oxidativestressiscloselyassociatedwithsecondarycelldeathinmanydisordersofthecentralnervoussystemincludingstroke,Parkinson’sdisease,Alzheimer’sdisease.Amongmanyaberrantoxidativestress-associatedproteins,DJ-1hasbeenassociatedwiththeoxidativestresscelldeathcascadeprimarilyinParkinson’sdisease.Althoughprincipallyexpressedinthecytoplasmandnucleus,DJ-1canbesecretedintotheserumunderpathologicalcondition.Recently,aclosepathologicalassociationbetweenDJ-1andoxidativestressinstrokehasbeenimplicated.Tothisend,weandothershavedemonstratedtheimportantroleofmitochondriainneuroprotectionforstrokebydemonstratingthatthetranslocationofDJ-1inthemitochondriacouldpotentiallymitigatemitochondrialinjury.Here,wediscussourrecentfindingstestingthehypothesisthatDJ-1notonlyfunctionsasaformofintracellularprotectionfromoxidativestress,butthatitalsoutilizesparacrineand/orautocrinecuesinordertoaccomplishextracellularsignalingbetweenneighboringneuronalcells,resultinginneuroprotection.ThisarticlehighlightsrecentevidencesupportingthestatusofDJ-1askeyanti-oxidativestresstherapeutictargetforstroke.

简介：TheRho/Rho-associatedcoiled-coilcontainingproteinkinase(Rho/ROCK)pathwayisamajorsignalingpathwayinthecentralnervoussystem,transducinginhibitorysignalstoblockregeneration.Aftercentralnervoussystemdamage,themaincauseofimpairedregenerationisthepresenceoffactorsthatstronglyinhibitregenerationinthesurroundingmicroenvironment.ThesefactorssignalthroughtheRho/ROCKsignalingpathwaytoinhibitregeneration.Therefore,athoroughunderstandingoftheRho/ROCKsignalingpathwayiscrucialforadvancingstudiesonregenerationandrepairoftheinjuredcentralnervoussystem.

简介：Regenerationinthecentralnervoussystem(CNS)islimited,andCNSdamageoftenleadstocognitiveimpairmentorpermanentfunctionalmotorandsensoryloss.Impairedregenerativecapacityismultifactorialandincludesinflammation,lossofthebloodbrainbarrier,andalterationintheextracellularmatrix(ECM).OneofthemainproblemsistheformationofaglialscarandtheproductionofinhibitoryECM,suchasproteoglycans,that

简介：Age-relatedmaculardegeneration(AMD)causesirreversiblelossofcentralvisionforwhichthereisnoeffectivetreatment.IncipientpathologyisthoughttooccurintheretinaformanyyearsbeforeAMDmanifestsfrommidlifeonwardstoaffectalargeproportionoftheelderly.Althoughgeneticaswellasnon-genetic/environmentalrisksarerecognized,itscomplexaetiologymakesitdifficulttoidentifysusceptibility,orindeedwhattypeofAMDdevelopsorhowquicklyitprogressesindifferentindividuals.HerewesummarizetheliteraturedescribinghowtheAlzheimer's-linkedamyloidbeta(Aβ)groupofmisfoldingproteinsaccumulateintheretina.ThediscoveryofthiskeydriverofAlzheimer'sdiseaseinthesenescentretinawasunexpectedandsurprising,enablinganaltogetherdifferentperspectiveofAMD.WearguethatAβfundamentallydiffersfromothersubstanceswhichaccumulateintheageingretina,anddiscussourlatestfindingsfromamousemodelinwhichphysiologicalamountsofAβweresubretinally-injectedtorecapitulatesalientfeaturesofearlyAMDwithinashortperiod.OurdiscoveriesaswellasthoseofotherssuggestthepatternofAβaccumulationandpathologyindonoraged/AMDtissuesarecloselyreproducedinmice,includinglate-stageAMDphenotypes,whichmakesthemhighlyattractivetostudydynamicaspectsofAβ-mediatedretinopathy.Furthermore,wediscussourfindingsrevealinghowAβbehavesatsingle-cellresolution,andconsiderthelong-termimplicationsforneuroretinalfunction.WeproposeAβasakeyelementinswitchingtoadiseasedretinalphenotype,whichisnowbeingusedasabiomarkerforlatestageAMD.

简介：Thereceptorforadvancedglycationendproducts(RAGE)isareceptoroftheimmunoglobulinsuperfamilyofcellsurfacemoleculeswhichplaysimportantcontributionsunderbothphysiologicalandpathologicalconditions.OvertheyearsextensiveresearchworksupportedthedetrimentalroleofRAGEinAlzheimer’sdisease(AD)pathophysiology,rangingfromitsinvolvementinbetaamyloid(Aβ)braininfluxandclearance,

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简介：WithintheCNSnuclearfactor-kappaB(NF-κB)transcriptionfactorsareinvolvedinawiderangeoffunctionsbothinhomeostasisandinpathology.Overtheyears,ourandothergroupsproducedavastarrayofinformationonthecomplexinvolvementofNF-κBproteinsindifferentaspectsofpostnatalneurogenesisInparticular,severalextracellularsignalsandmembranereceptorshavebeenidentifiedasbeingabletoaffectneuralprogenitorcells(NPC)andtheirprogenyviaNF-κBactivation.AcrucialroleintheregulationofneuronalfatespecificationinadulthippocampalNPCisplayedbytheNF-κBp50subunit.NF-κBp50KOmicedisplayaremarkablereductioninadulthippocampalneurogenesiswhichcorrelateswithaselectivedefectinhippocampal-dependentshort-termmemory.MoreoverabsenceofNF-κBp50canprofoundlyaffecttheinvitroproneurogenicresponseofadulthippocampalNPC(ahNPC)toseveralendogenoussignalsanddrugs.HereinwebrieflyreviewthecurrentknowledgeonthepivotalroleofNF-κBp50intheregulationofadulthippocampalneurogenesis.InadditionwediscussmorerecentdatathatfurtherextendtherelevanceofNF-κBp50tonovelastroglia-derivedsignalswhichcaninfluenceneuronalspecificationofahNPCandtoastrocyte-NPCcross-talk.