grant
Disentangling the HIV/opioid intertwined mechanisms on mitochondrial mediated inflammasome activation, neurotoxicity and targeting strategies: In vivo and in vitro analyses of fresh human brain
Organization UNIVERSITY OF CALIFORNIA, SAN DIEGOLocation LA JOLLA, UNITED STATESPosted 15 Apr 2025Deadline 31 Jan 2030
NIHUS FederalResearch GrantFY2026AIDS VirusAIDS focused researchAIDS related researchAIDS researchAIDS scienceAIDS specific researchAcquired Immune Deficiency Syndrome VirusAcquired Immunodeficiency Syndrome VirusAddressAltruismAmmon HornAnalgesic AgentsAnalgesic DrugsAnalgesic PreparationAnalgesicsAnodynesAnti-Retroviral AgentsAntibodiesAntinociceptive AgentsAntinociceptive DrugsApoptosis-Related Cysteine Protease Caspase 1ArchivesAssayAutopsyBasal GangliaBasal NucleiBeta Proprotein Interleukin 1BioassayBiological AssayBiometricsBiometryBiostatisticsBody TissuesBrainBrain Nervous SystemBrain regionCASP-1CASP1CASP1 geneCNS Nervous SystemCaspase-1Caspase-1 GeneCell BodyCell Culture TechniquesCellsCentral Nervous SystemCessation of lifeChronicCognitive DisturbanceCognitive ImpairmentCognitive declineCognitive function abnormalCollectionComplexConsequences of HIVCornu AmmonisDataDeathDevelopmentDisturbance in cognitionEncephalonEnrollmentEvaluationExhibitsExposure toFreezingGC MSGCMSGas-Liquid-Mass Spectrometry ChromatographyGene TranscriptionGenetic TranscriptionGiftsGoalsHIVHIV Envelope Glycoprotein gp120HIV Envelope Protein gp120HIV InfectionsHIV disease transmissionHIV env Protein gp120HIV focused researchHIV individualsHIV infected individualsHIV infected personsHIV infection spreadHIV infection transmissionHIV investigationHIV peopleHIV positive individualsHIV positive peopleHIV related cognitive dysfunctionHIV related cognitive impairmentHIV related researchHIV researchHIV scienceHIV specific researchHIV spreadHIV transmissionHIV viral infectionHIV viral transmissionHIV virus infectionHIV-1 infectionHIV-1 spreadHIV-1 transmissionHIV-1 virus transmissionHIV-associated cognitive dysfunctionHIV-associated cognitive impairmentHIV/AIDS transmissionHTLV-III gp120HealthHealth PromotionHippocampusHistoryHumanHuman Immunodeficiency Virus Type 1 transmissionHuman Immunodeficiency VirusesICE ProteaseIFN-Gamma-Inducing Factor GeneIFN-gamma-Inducing FactorIGIFIGIF GeneIL-1 GammaIL-1 Gamma GeneIL-1 betaIL-1 beta ConvertaseIL-1 beta-Converting EnzymeIL-1 βIL-1-bIL-18IL-18 GeneIL-1BCIL-1b Converting EnzymeIL-1gIL-1g GeneIL-1βIL1-BetaIL1-βIL18IL18 ProteinIL18 geneIL1B ProteinIL1B-ConvertaseIL1BCIL1BCEIL1F2IL1F4IL1F4 GeneIL1βImmunoblottingImpaired cognitionIn VitroIndividualInfection by HIV-1Infection from HIV-1Infection of HIV-1InflammasomeInflammationInfumorphInterferon-Gamma-Inducing Factor GeneInterferon-gamma-Inducing FactorInterleukin 1-B Converting EnzymeInterleukin 1-Beta ConvertaseInterleukin 18 (Interferon-Gamma-Inducing Factor)Interleukin 18 (Interferon-Gamma-Inducing Factor) GeneInterleukin 18 ProproteinInterleukin 18 Proprotein GeneInterleukin 1betaInterleukin-1 Beta Converting EnzymeInterleukin-1 Converting EnzymeInterleukin-1 GammaInterleukin-1 Gamma GeneInterleukin-1 betaInterleukin-18Interleukin-18 PrecursorInterleukin-18 Precursor GeneInterleukin-1βInterventionInvestigationInvestigation on HIVKadianKnowledgeLAV-HTLV-IIILong-term infectionLymphadenopathy-Associated VirusMGC12320MGC12320 GeneMS ContinMSirMass FragmentographiesMass FragmentographyMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMass-Gas Chromatography SpectrometryMass-Gas Chromatography Spectrum AnalysisMeasuresMediatingMediatorMethodologyMicroscopicMitochondriaModelingModern ManMorphiaMorphineMyeloid CellsNerve CellsNerve DegenerationNerve UnitNeural CellNeuraxisNeurocyteNeurologicNeurologicalNeuron DegenerationNeuronsNeuropsychologiesNeuropsychologyNon-Polyadenylated RNAOccipital lobeOpiatesOpioidOramorphOramorph SROutcomePLWHPWHParietal LobeParticipantPathway interactionsPatternPersonsPharmacologyPreinterleukin 1 BetaProteinsRNARNA ExpressionRNA Gene ProductsRNA SplicingRecording of previous eventsResearchResearch SpecimenRibonucleic AcidRoxanolSalutogenesisShort interfering RNASmall Interfering RNASpecimenSplicingStatex SRTherapeuticTissuesTranscriptionTubulinViralVirus-HIVWestern BlottingWestern Immunoblottingaltruisticanti-retroviralantiretroviral therapyantiretroviral treatmentbrain cellbrain tissuecatalystcell culturecell cultureschronic infectioncognitive assessmentcognitive dysfunctioncognitive functioncognitive losscognitive testingcohortdevelopmentalenrollextracellularfrontal cortexfrontal lobegp120gp120 ENV Glycoproteingp120(HIV)hippocampalhistorieshuman immunodeficiency virus infectionhuman immunodeficiency virus researchhuman immunodeficiency virus transmissionimprovedin vitro Modelin vivoindividuals infected with HIVindividuals with HIVindividuals with human immunodeficiency virusinfected with HIVinfected with human immunodeficiency virusinsightion trap mass spectrometryknock-downknockdownlicit opioidmass fragmentometrymilligrammitochondrialnecropsyneural degenerationneural inflammationneurodegenerationneurodegenerativeneuroinflammationneuroinflammatoryneurological degenerationneuron toxicityneuronalneuronal degenerationneuronal toxicityneuropathologicneuropathologicalneuropathologyneuroprotectionneuroprotectiveneuropsychologicneurotoxicneurotoxicityoccipital cortexopiate consumptionopiate drug useopiate exposureopiate intakeopiate medicationopiate useopioid consumptionopioid drug useopioid exposureopioid intakeopioid medicationopioid usepain killerpain medicationpain relieverpainkillerparietal cortexparticipant enrollmentpathwaypatient enrollmentpeople infected with HIVpeople infected with human immunodeficiency viruspeople living with HIVpeople with HIVpeople with human immunodeficiency viruspersistent infectionpostmortemprescribed opiateprescribed opioidprescription opiateprescription opioidpromoting healthprotein blottingresearch addressing HIVresearch in HIVresearch into HIVresearch on HIVresearch on human immunodeficiency virusresearch to address HIVresponsescience on HIVscience to address HIVsiRNAsmall moleculespread of human immunodeficiency virusstudies on HIVsynergismvirology
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Summary.
Despite effective antiretrovirals (ARV), Human Immunodeficiency Virus (HIV) spreads within the central nervous
system (CNS) and establishes persistent infection precipitating cognitive impairment (CI). Recent findings
suggest that HIV protein (namely VPR) expression in the brain activates the inflammasome pathway in neurons
leading to…
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