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1、NIHPublicAccessAuthorManuscriptJNeuroimmunol.Authormanuscript;availableinPMC2012September15.NIH-PAAuthorManuscriptPublishedinfinaleditedformas:NIH-PAAuthorManuscriptNIH-PAAuthorManuscriptJNeuroimmunol.2011September15;238(1-2):1±11.doi:10.1016/j.jneuroim.2011.07.002.Inflammationintheearlystagesof
2、neurodegenerativepathologyPreetiJ.Khandelwal1,AlexanderM.Herman1,andCharbelE-HMoussa11DepartmentofNeuroscience,GeorgetownUniversityMedicalCenter.WashingtonD.C.U.S.A.20007AbstractInflammationissecondarytoproteinaccumulationinneurodegenerativediseases,includingAlzheimer’s,Parkinson’sandAmyotrophic
3、LateralSclerosis.Emergingevidenceindicatesustainedinflammatoryresponses,involvingmicrogliaandastrocytesinanimalmodelsofneurodegeneration.ItisunknownwhetherinflammationisbeneficialordetrimentaltodiseaseprogressionandhowinflammatoryresponsesareinducedwithintheCNS.Persistenceofaninflammatorystimulu
4、sorfailuretoresolvesustainedinflammationcanresultinpathology,thus,mechanismsthatcounteractinflammationareindispensable.Herewereviewstudiesoninflammationmediatedbyinnateandadaptiveimmunityintheearlystagesofneurodegenerationandhighlightimportantareasforfutureinvestigation.Keywordsneuro-inflammatio
5、n;neurodegeneration;fractlakine;TRAILIntroductionTheimmunesystemisessentialforthemaintenanceoftissuehomeostasisandtheresponsetoinfectionandinjury.Microglia,atypeofglialcells,aremacrophagesthatareresidentinthecentralnervoussystem(CNS)andthemajorresidentimmunecellsinthebrain,wheretheyprovideinnate
6、immunity(RansohoffandPerry,2009).Innormalbrains,microgliashowramified,highlymotileprocessesundergoingcyclesofprotrusion,extension,andwithdrawalallowingthemtomonitorthelocalmicroenvironmentanddetectCNSdamage(Nimmerjahnetal.,2005).Microgliareleasefactorsthatinfluenceanothertypeofsupportglialcells,
7、calledastrocytes,aswellasneurons.Underphysiologicalconditions,microgliaaredeactivatedandtheyprovideinnateimmunity,producinganti-inflammatoryandneurotrophicfactors(Streit,2002).Understress,includingpathogeninvasion,injuryorab
