cGAS-STING信号通路在先天性免疫中的作用研究进展-豆柴文库

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cGAS-STING信号通路在先天性免疫中的作用研究进展
Title:AdvancesintheRoleofthecGAS-STINGSignalingPathwayinInnateImmunity
Introduction:
ThecGAS-STINGsignalingpathwayisacrucialcomponentoftheinnateimmunesystemthatplaysapivotalroleininitiatingandactivatingtheimmuneresponseagainstvariouspathogens.ThispathwayisinvolvedinthedetectionofcytosolicDNAandsubsequentproductionoftypeIinterferonsandproinflammatorycytokines.Inrecentyears,significantprogresshasbeenmadeinunderstandingthemolecularmechanismsandfunctionsofthecGAS-STINGsignalingpathway,highlightingitsimportanceinthefieldofinnateimmunity.ThispaperaimstoprovideanoverviewoftherecentadvancementsintheroleofthecGAS-STINGsignalingpathwayininnateimmunity.
1.DiscoveryandActivationofcGAS-STINGSignalingPathway:
ThecGAS-STINGsignalingpathwaywasdiscoveredasacytosolicDNA-sensingpathwaythatdetectsmicrobialandself-DNA,resultingintheproductionoftypeIinterferons(IFNs).ThecyclicGMP-AMPsynthase(cGAS)enzymeplaysacrucialroleinsensingcytosolicDNA,whilethestimulatorofinterferongenes(STING)actsasthedownstreameffector.UponbindingtoDNA,cGASsynthesizescyclicGMP-AMP(cGAMP),whichthenbindsandactivatesSTING,leadingtotheactivationofdownstreamsignalingcascadesinvolvedinimmuneresponses.
2.MolecularMechanismsofcGAS-STINGPathwayActivation:
VariousstudieshaveunraveledtheintricatemolecularmechanismsunderlyingtheactivationandregulationofthecGAS-STINGsignalingpathway.ThisincludestheidentificationofdirectDNAbindingandcatalyticdomainsofcGAS,aswellastheelucidationoftheconformationalchangesthatoccuruponDNAbinding.Additionally,post-translationalmodificationsofSTING,suchasphosphorylationandpalmitoylation,regulateitsactivationandsubcellularlocalization.
3.RoleofcGAS-STINGSignalingPathwayinInnateImmuneDefense:
ThecGAS-STINGpathwayactsasacriticalmediatorofinnateimmunedefenseagainstviral,bacterial,andparasiticinfections.StudieshavedemonstratedthatthecGAS-STINGpathwayisresponsiblefortheproductionoftypeIinterferons,proinflammatorycytokines,andtheinductionofantiviralgenes.Furthermore,activationo