Nervegrowthfactor(NGF)isoneofafamilyofneurotrophinsthatinducethesurvivalandproliferationofneurons.IncellcultureNGFinducestheformationofneuriteprojectionsandinvivomaystimulatetheinnervationoftissues.NGFplaysaroleintherepair,regeneration,andprotectionofneurons,andassuchcouldserveasatherapeuticagentinneurodegenerativeconditionssuchasAlzheimer"sdisease.OnepotentialmethodofNGFapplicationwouldbethroughgenetherapyorthroughimplantationofcellsthathavebeengeneticallymodifiedexvivo.NGFhasalsobeensuggestedtoplayaroleinotherphysiologicalsystemsandtissuessuchastheimmunesystem.NGFhastworeceptors,TrkAandthep75(NTR).NGFmaysignalitsneuroprotectiveactionsthroughthetyrosinekinaseTrkAreceptorandtriggerapoptosisinsomecellsthroughthep75receptor.High-affinitybindingofNGFrequiresbothTrkAandp75(NTR).BindingofNGFtotheTrkAreceptorcausesactivationofthereceptortyrosinekinaseanddownstreamsignalingcascades.OneofthedownstreamsignalingpathwaysofNGFactivatesphospholipaseC,releasingDAGandIP3andactivatingassociateddownstreampathwayssuchasproteinkinaseC.AnotherNGF-activatedpathwayistheras-mediatedactivationofthemapkinasepathway.ThispathwayisinitiatedthroughrecruitmentandactivationofShc,whichleadstorasactivationthroughGrb-2andSos-1.TheMapkinasecascadeincludesraf,MekandErk.ThedownstreameffectorsoftheraspathwayincludeactivationoffosandjuntoformAP-1,activatinggenesthroughthistranscriptionfactor.OthertranscriptionfactorsinvolvedinNGFresponsesincludeEgrandCREB.TheEgrfamilyoftranscriptionfactorsaswellastheMek/ErkpathwaycontributetoNGF-inducedneuriteformation.TheCREBfamilyoftranscriptionfactorsareinvolvedinNGF-inducedsurvivalofsympatheticneurons.FurtherunderstandingofNGFsignalingmaybeappliedtothemodulationofNGFresponsesinneurodegenerativeconditions.

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