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1、ReviewTRENDSinNeurosciencesVol.30No.11NeuronalOnandOffsignalscontrolmicroglia1231KnutBiber,HaraldNeumann,KazuhideInoueandHendrikusW.G.M.Boddeke1DepartmentofMedicalPhysiology,UniversityMedicalCenterGroningen(UMCG),UniversityofGroningen,Groningen,9713AV,TheNetherlands2InstituteofReconstru
2、ctiveNeurobiology,LIFE&BRAINCenter,UniversityofBonn,53127Bonn,Germany3DepartmentofMolecularandSystemPharmacology,GraduateSchoolofPharmaceuticalSciences,KyushuUniversity,Fukuoka,812-8582,JapanRecentfindingsindicatethatneuronsarenotmerely(IL)-4inducedaneuroprotectivephenotype[10],whichpass
3、ivetargetsofmicrogliabutrathercontrolmicroglialcorroboratesmanyearlierinvitrofindingsthatconcernactivity.Thevarietyofdifferentsignalsthatneuronsuseneuroprotectivemicrogliaactivity(forareview,see[1,2]).tocontrolmicrogliacanbedividedintotwocategories:Also,numerousneuroprotectiveeffectsofac
4、tivatedmicro-Offsignalsconstitutivelykeepmicrogliaintheirrestinggliahavebeendemonstratedrecentlyinvivo.Microgliaarestateandantagonizeproinflammatoryactivity.Onsig-beneficialinamodelofnitricoxide(NO)-dependentexci-nalsareinducibleandincludepurines,chemokines,totoxicity[11]andinanimalmodels
5、ofstroke[12],aswellglutamate.Theyinstructmicrogliaactivationunderasinmousemodelsofamyotrophiclateralsclerosis(ALS)pathologicalconditionstowardsabeneficialordetri-[13]andofAlzheimer’sdisease[14].mentalphenotype.Variousneuronalsignalingmol-Bycontrast,microglialneurotoxicitycanoccurafterecu
6、lesthusactivelycontrolmicrogliafunction,therebyexcessiveanduncontrolledstimulationofmicrogliacontributetotheinflammatorymilieuofthecentral[7,15]orwhenmicrogliafunctionisimpaired[13,16,17].nervoussystem.Thus,neuronsshouldbeenvisagedInterestingly,mutationsofthemicroglialproteinslikeaskeyim
7、munemodulatorsinthebrain.triggeringreceptorexpressedonmyeloidcells-2(TREM2)orDNAXactivatingproteinof12kDa(DAP12)areMicroglia:thefirstlineofdefensemostlikelyinstrumentalforthedevelopmentofaneuro-Disturbancesorthreatstocentralnervoussystem(CNS)degenerativediseasecalledNasu-Hakolao