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Roflupram通过促进自噬减轻Aβ25-35诱导的小胶质细胞活化作用研究.docx

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Roflupram通过促进自噬减轻Aβ25-35诱导的小胶质细胞活化作用研究 Roflupramisaselectivephosphodiesterase4(PDE4)inhibitor,whichhasshownpotentialinreducingneuroinflammationandneuronaldamageinneurodegenerativediseasessuchasAlzheimer'sdisease(AD).AkeypathologicalhallmarkofADistheaccumulationofamyloid-beta(Aβ)peptides,leadingtotheactivationofglialcellsandneuroinflammation.Inthisstudy,weaimtoinvestigatetheroleofRoflupraminpromotingautophagytoalleviateAβ25-35-inducedmicroglialactivation. Microglialcells,theresidentimmunecellsofthecentralnervoussystem(CNS),playacrucialroleinmaintaininghomeostasisanddefendingagainstpathologicalinsults.However,chronicactivationofmicrogliacanleadtothereleaseofpro-inflammatorycytokinesandchemokines,resultinginneuroinflammationandneuronaldamage.Autophagy,ahighlyregulatedcellularprocess,isinvolvedinthedegradationandrecyclingofdamagedproteinsandorganelles.Dysregulationofautophagyhasbeenimplicatedinthepathogenesisofvariousneurodegenerativediseases,includingAD. Aβ25-35isaneurotoxicfragmentderivedfromtheamyloidprecursorprotein(APP),whichhasbeenwidelyusedtoinduceneuroinflammationandoxidativestressininvitroandinvivoADmodels.Inourstudy,wetreatedmicroglialcellswithAβ25-35tosimulatetheinflammatoryresponseinAD.WethenevaluatedtheeffectsofRoflupramonAβ25-35-inducedmicroglialactivationandautophagy. First,weassessedtheviabilityofmicroglialcellsfollowingtreatmentwithdifferentconcentrationsofAβ25-35.Cellviabilitywassignificantlyreducedinadose-dependentmanner,indicatingthecytotoxicityofAβ25-35.Next,weinvestigatedtheeffectsofRoflupramonmicroglialactivationbymeasuringtheexpressionofpro-inflammatorycytokines,suchasinterleukin-1β(IL-1β)andtumornecrosisfactor-alpha(TNF-α),usingquantitativereal-timepolymerasechainreaction(qRT-PCR)andenzyme-linkedimmunosorbentassay(ELISA).RoflupramtreatmentresultedinasignificantdecreaseintheexpressionandsecretionofIL-1βandTNF-α,suggestingitsanti-inflammatoryproperties. Tofurtherelucidatetheunderlyingmechanisms,weexaminedtheeffectofRoflupramonautophagyinduction.We