2021
TCA cycle metabolic compromise due to an aberrant S-nitrosoproteome in HIV-associated neurocognitive disorder with methamphetamine use
Doulias P, Nakamura T, Scott H, McKercher S, Sultan A, Deal A, Albertolle M, Ischiropoulos H, Lipton S. TCA cycle metabolic compromise due to an aberrant S-nitrosoproteome in HIV-associated neurocognitive disorder with methamphetamine use. Journal Of NeuroVirology 2021, 27: 367-378. PMID: 33876414, PMCID: PMC8477648, DOI: 10.1007/s13365-021-00970-4.Peer-Reviewed Original ResearchConceptsNeurocognitive disordersMeth usePathogenesis of HIVHuman postmortem brainAberrant protein S-nitrosylationCNS pathologyControl brainsSynaptic damageS-nitrosylationHIV-1Metabolic compromisePostmortem brainsMethamphetamine useNitric oxideDrug abuseRedox stressNitrosative stressBrainHIVProtein S-nitrosylationDisordersS-nitrosoproteomeSystematic inhibitionTCA cycle enzymesPathogenesis
2006
HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection
Kaul M, Ma Q, Medders K, Desai M, Lipton S. HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection. Cell Death & Differentiation 2006, 14: 296-305. PMID: 16841089, DOI: 10.1038/sj.cdd.4402006.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virus-1Neuronal cell deathStromal cell-derived factor-1HIV-1 envelope glycoprotein gp120Cell-derived factor-1Cell deathHIV-1 coreceptor CCR5Chemokine receptor CCR5Immunodeficiency virus-1Brain-derived cellsEnvelope glycoprotein gp120Intracellular free Ca2Gp120 neurotoxicityCCR5 ligandsHIV coreceptorsP38 mitogen-activated protein kinaseCCR5 agonistsNeuroprotective pathwaysReceptor CCR5Heterologous desensitizationCoreceptor CCR5CXCR4 agonistCCR5Glial culturesGlycoprotein gp120
2005
HIV-1 infection and AIDS: consequences for the central nervous system
Kaul M, Zheng J, Okamoto S, Gendelman H, Lipton S. HIV-1 infection and AIDS: consequences for the central nervous system. Cell Death & Differentiation 2005, 12: 878-892. PMID: 15832177, DOI: 10.1038/sj.cdd.4401623.Peer-Reviewed Original ResearchMeSH KeywordsAcquired Immunodeficiency SyndromeAIDS Dementia ComplexAnimalsAntiretroviral Therapy, Highly ActiveApoptosisApoptosis Regulatory ProteinsBrainChemokinesForecastingHIV Envelope Protein gp120HIV-1HumansMembrane GlycoproteinsMicrogliaNerve DegenerationNeuronsReceptors, ChemokineSignal TransductionStem CellsTNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor-alphaConceptsHuman immunodeficiency virus-1Glutamate receptor-mediated excitotoxicityReceptor-mediated excitotoxicityHIV-1 infectionImmune competent cellsExtracellular matrix-degrading enzymesImmunodeficiency virus-1Central nervous systemFuture therapeutic interventionsMatrix-degrading enzymesFrank dementiaInflammatory mediatorsNeuronal damageMotor dysfunctionChemokine receptorsGlial functionDegenerative mechanismsNeurological problemsParticular macrophagesBehavioral abnormalitiesNervous systemTherapeutic interventionsNeuropathological responsesVirus 1InfectionExperimental and potential future therapeutic approaches for HIV-1 associated dementia targeting receptors for chemokines, glutamate and erythropoietin
Kaul M, Lipton S. Experimental and potential future therapeutic approaches for HIV-1 associated dementia targeting receptors for chemokines, glutamate and erythropoietin. Neurotoxicity Research 2005, 8: 167-186. PMID: 16260394, DOI: 10.1007/bf03033828.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virus-1Central nervous systemGlutamate receptor-mediated excitotoxicityHIV-1 infection resultsPotential future therapeutic approachesReceptor-mediated excitotoxicityImmune competent cellsExtracellular matrix-degrading enzymesFuture therapeutic approachesImmunodeficiency virus-1Future therapeutic strategiesMatrix-degrading enzymesFrank dementiaInflammatory mediatorsNeuronal damageMotor dysfunctionChemokine receptorsEffective therapyGlial functionPathologic mechanismsTherapeutic approachesNeurological problemsTherapeutic strategiesInfection resultsParticular macrophages
2004
Signaling pathways to neuronal damage and apoptosis in human immunodeficiency virus type 1-associated dementia: Chemokine receptors, excitotoxicity, and beyond
Kaul M, Lipton S. Signaling pathways to neuronal damage and apoptosis in human immunodeficiency virus type 1-associated dementia: Chemokine receptors, excitotoxicity, and beyond. Journal Of NeuroVirology 2004, 10: 97-101. PMID: 14982746, DOI: 10.1080/753312759.Peer-Reviewed Original ResearchConceptsNeuronal damageChemokine receptorsN-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicityHuman immunodeficiency virus-1 (HIV-1) infectionHuman immunodeficiency virus type 1Immunodeficiency virus type 1Applicable therapeutic interventionReceptor-mediated excitotoxicityVirus-1 infectionVirus type 1HIV infectionInflammatory factorsHIV-1Therapeutic interventionsType 1Downstream mechanismsExcitotoxicityDementiaInfectionReceptorsNeuropathologyPathwayDamage
2001
Pathways to neuronal injury and apoptosis in HIV-associated dementia
Kaul M, Garden G, Lipton S. Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 2001, 410: 988-994. PMID: 11309629, DOI: 10.1038/35073667.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virus-1Neuronal injuryRelease of macrophageImmunodeficiency virus-1Direct injuryTherapeutic interventionsAlarming occurrenceNeurodegenerative diseasesInjuryVirus 1NeuronsDementiaViral proteinsMacrophagesFree radicalsApoptosisToxinPathwayExcitotoxicityMicrogliaHIVDiseaseBrain
2000
Cytokine-Stimulated, But Not HIV-Infected, Human Monocyte-Derived Macrophages Produce Neurotoxic Levels of l-Cysteine
Yeh M, Kaul M, Zheng J, Nottet H, Thylin M, Gendelman H, Lipton S. Cytokine-Stimulated, But Not HIV-Infected, Human Monocyte-Derived Macrophages Produce Neurotoxic Levels of l-Cysteine. The Journal Of Immunology 2000, 164: 4265-4270. PMID: 10754324, DOI: 10.4049/jimmunol.164.8.4265.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCerebral CortexCysteineCytokinesDose-Response Relationship, ImmunologicHIV Envelope Protein gp120HIV-1HumansImmune SeraInterleukin 1 Receptor Antagonist ProteinInterleukin-1Macrophage ActivationMacrophagesMonocytesNeuronsRatsRats, Sprague-DawleyReceptors, Interleukin-1Receptors, N-Methyl-D-AspartateSialoglycoproteinsSphingosineTumor Necrosis Factor-alphaConceptsHuman monocyte-derived macrophagesNeuronal injuryTNF-alphaHIV-1N-methyl-D-aspartate (NMDA) subtypeUninfected cellsMacrophages/microgliaCultured rat cerebrocortical neuronsVirus-infected macrophagesRelease of neurotoxinsRat cerebrocortical neuronsEnvelope glycoprotein gp120Monocyte-derived macrophagesDose-dependent mannerNeuropathological symptomsIL-1betaGlutamate receptorsCerebrocortical neuronsHIVGlycoprotein gp120Mononuclear phagocytesNeurotoxic levelsGp120Human monocytesCytokine stimulation
1999
Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis
Kaul M, Lipton S. Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8212-8216. PMID: 10393974, PMCID: PMC22214, DOI: 10.1073/pnas.96.14.8212.Peer-Reviewed Original ResearchMeSH KeywordsAIDS Dementia ComplexAnimalsApoptosisCells, CulturedCerebral CortexChemokine CCL4Chemokine CCL5Chemokine CXCL12ChemokinesCytokinesEmbryo, MammalianHIV Envelope Protein gp120HIV-1HumansImmunoglobulin FragmentsMacrophage ActivationMacrophage Inflammatory ProteinsMacrophagesNeurogliaNeuronsOligopeptidesRatsRats, Sprague-DawleyRecombinant ProteinsT-LymphocytesConceptsMacrophages/microgliaNeuronal apoptosisChemokine receptorsSDF-1Brain macrophages/microgliaStromal cell-derived factorRat cerebrocortical culturesBeta-chemokines RANTESCell-derived factorNeurotoxic factorsP38 mitogen-activated protein kinase (MAPK) pathwayProportion of cellsInflammatory proteinP38 mitogen-activated protein kinaseGp120SF2Cerebrocortical culturesReceptor CXCR4MicrogliaHuman neuronsHIV gp120CXCR4 receptorMitogen-activated protein kinase pathwayMitogen-activated protein kinaseNeuronsGp120The contribution of various NOS gene products to HIV-1 coat protein (gp120)-mediated retinal ganglion cell injury.
Dreyer E, Zurakowski D, Gorla M, Vorwerk C, Lipton S. The contribution of various NOS gene products to HIV-1 coat protein (gp120)-mediated retinal ganglion cell injury. Investigative Ophthalmology & Visual Science 1999, 40: 983-9. PMID: 10102296.Peer-Reviewed Original ResearchConceptsNitric oxide synthaseHIV-1 coat proteinRetinal ganglion cell injuryIsoforms of NOSNitric oxideNeuronal nitric oxide synthaseGanglion cell injuryRetinal ganglion cellsPresence of nNOSNOS-deficient miceWild-type miceNeuronal lossExcitotoxic pathwayIntravitreal injectionGanglion cellsGp120 toxicityNeuronal pathologyNOS inhibitorOxide synthaseHIV-1Cell injuryControl animalsNervous systemGp120Pathologic states
1998
NEURONAL INJURY ASSOCIATED WITH HIV-1: Approaches to Treatment
Lipton S. NEURONAL INJURY ASSOCIATED WITH HIV-1: Approaches to Treatment. The Annual Review Of Pharmacology And Toxicology 1998, 38: 159-177. PMID: 9597152, DOI: 10.1146/annurev.pharmtox.38.1.159.Peer-Reviewed Original ResearchConceptsNeuronal injuryNeuronal damageHIV-1-associated cognitive/motor complexN-methyl-D-aspartate (NMDA) receptor-operated channelsCognitive/motor complexAIDS dementia complexHIV-1 resultsHIV-1 infectionExistence of HIVBrains of patientsReceptor-operated channelsFuture pharmacological interventionsFinal common pathwayPlatelet-activating factorFree radicalsAIDS dementiaReactive astrocytesDementia complexCognitive dysfunctionNMDA antagonistsExcessive activationNeuronal susceptibilityPharmacological interventionsHIV-1Excessive influx
1996
Similarity of Neuronal Cell Injury and Death in AIDS Dementia and Focal Cerebral Ischemia: Potential Treatment with NMDA Open‐Channel Blockers and Nitric Oxide‐Related Species
Lipton S. Similarity of Neuronal Cell Injury and Death in AIDS Dementia and Focal Cerebral Ischemia: Potential Treatment with NMDA Open‐Channel Blockers and Nitric Oxide‐Related Species. Brain Pathology 1996, 6: 507-517. PMID: 8944320, DOI: 10.1111/j.1750-3639.1996.tb00879.x.Peer-Reviewed Original ResearchConceptsFocal cerebral ischemiaNeuronal cell deathAIDS dementiaNeuronal injuryCerebral ischemiaNeuronal damageCell injuryHIV-1-associated cognitive/motor complexN-methyl-D-aspartate (NMDA) receptor-operated channelsCognitive/motor complexNMDA open-channel blockersHIV-1 envelope protein gp120Cell deathHIV-1 resultsExistence of HIVNeuronal cell injuryReceptor-operated channelsFuture pharmacological interventionsFinal common pathwayEnvelope protein gp120Platelet-activating factorFree radicalsOpen channel blockerAIDS brainsIschemic core
1995
gp120 and neurotoxicity in vivo Consideration of animal models and technical methods in interpretation of negative data
Lipton S, Brenneman D, Silverstein F, Masliah E, Mucke L. gp120 and neurotoxicity in vivo Consideration of animal models and technical methods in interpretation of negative data. Trends In Pharmacological Sciences 1995, 16: 122. PMID: 7610496, DOI: 10.1016/s0165-6147(00)88998-1.Peer-Reviewed Original ResearchRegulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated neurological disease.
Bukrinsky M, Nottet H, Schmidtmayerova H, Dubrovsky L, Flanagan C, Mullins M, Lipton S, Gendelman H. Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated neurological disease. Journal Of Experimental Medicine 1995, 181: 735-745. PMID: 7530762, PMCID: PMC2191885, DOI: 10.1084/jem.181.2.735.Peer-Reviewed Original ResearchConceptsEffector cell functionInducible NO synthaseBrain tissueAIDS patientsHIV-1Human immunodeficiency virus (HIV) persistenceHuman immunodeficiency virus type 1Human monocytesNitric oxide synthase activityImmunodeficiency virus type 1HIV-macrophage interactionsPediatric AIDS patientsHIV-1 diseaseCell functionHIV-1 infectionMacrophage antigen presentationExpression of NOSOxide synthase activityVirus-infected macrophagesPostmortem brain tissueVirus type 1Productive viral replicationCultured human monocytesHIV encephalitisHIV replication
1994
Neuronal Injury Associated with HIV-1 and Potential Treatment with Calcium-Channel and NMDA Antagonists
Lipton S. Neuronal Injury Associated with HIV-1 and Potential Treatment with Calcium-Channel and NMDA Antagonists. Developmental Neuroscience 1994, 16: 145-151. PMID: 7705221, DOI: 10.1159/000112101.Peer-Reviewed Original ResearchConceptsNMDA antagonistsHIV-1HIV-1 envelope protein gp120Existence of HIVBrains of patientsCalcium channel antagonistsVoltage-dependent Ca2Receptor-operated channelsFuture pharmacological interventionsFinal common pathwayAmyotrophic lateral sclerosisEnvelope protein gp120Platelet-activating factorDemise of neuronsInjury AssociatedAIDS dementiaNeuronal injuryGlutamate reuptakeNeurological manifestationsGlutamate releaseImmunodeficiency syndromeChannel antagonistsPharmacological interventionsProtein gp120Lateral sclerosisThe neuropathogenesis of HIV-1 infection
Gendelman H, Lipton S, Tardieu M, Bukrinsky M, Nottet H. The neuropathogenesis of HIV-1 infection. Journal Of Leukocyte Biology 1994, 56: 389-398. PMID: 8083614, DOI: 10.1002/jlb.56.3.389.Peer-Reviewed Original ResearchConceptsCentral nervous system infectionHIV-1-infected macrophagesBrain tissue pathologyNervous system infectionHIV-1 infectionProductive viral replicationVirus-infected cellsHIV neuropathogenesisMononuclear phagocyte lineageSystem infectionHIV infectionNeuronal damageBrain macrophagesCNS diseaseGlial proliferationGiant cellsTissue pathologyViral replicationSoluble factorsNeurotoxic activityInfectionMacrophagesPhagocyte lineageHIVNeuropathogenesisHIV-related neuronal injury
Lipton S. HIV-related neuronal injury. Molecular Neurobiology 1994, 8: 181-196. PMID: 7999315, DOI: 10.1007/bf02780669.Peer-Reviewed Original ResearchConceptsArachidonic acidExistence of HIVCalcium channel antagonistsVoltage-dependent Ca2Receptor-operated channelsFuture pharmacological interventionsFinal common pathwayAmyotrophic lateral sclerosisPlatelet-activating factorDysfunction of cognitionDemise of neuronsNeuropathic painAdult patientsAIDS dementiaNeuronal injuryNeurological manifestationsNeuronal damageImmunodeficiency syndromeAIDS patientsChannel antagonistsNMDA antagonistsNeuronal susceptibilityPharmacological interventionsLateral sclerosisParkinson's diseaseHIV displays its coat of arms
Lipton S. HIV displays its coat of arms. Nature 1994, 367: 113-114. PMID: 8114907, DOI: 10.1038/367113a0.Peer-Reviewed Original ResearchLaboratory basis of novel therapeutic strategies to prevent HIV-related neuronal injury.
Lipton S. Laboratory basis of novel therapeutic strategies to prevent HIV-related neuronal injury. Proceedings Of The Association For Research In Nervous And Mental Disease 1994, 72: 183-202. PMID: 8115713.Peer-Reviewed Original Research
1991
Calcium channel antagonists and human immunodeficiency virus coat protein–mediated neuronal injury
Lipton S. Calcium channel antagonists and human immunodeficiency virus coat protein–mediated neuronal injury. Annals Of Neurology 1991, 30: 110-114. PMID: 1656845, DOI: 10.1002/ana.410300121.Peer-Reviewed Original ResearchConceptsVoltage-dependent calcium channelsCalcium channel antagonistsNeuronal injuryChannel antagonistsCalcium channelsHuman immunodeficiency virus type 1 (HIV-1) envelope proteinImmunodeficiency syndrome dementia complexRat retinal ganglion cellsSubsequent neuronal injuryNeuronal calcium channelsRetinal ganglion cellsVoltage-dependent Ca2Mammalian central neuronsChannel antagonist drugsNeuronal damageDementia complexMaximal doseCentral neuronsGanglion cellsDihydropyridine classIntracellular calciumAntagonist drugsElectrophysiological studiesLow micromolar concentrationsGp120HIV‐Related Neurotoxicity
Lipton S. HIV‐Related Neurotoxicity. Brain Pathology 1991, 1: 193-199. PMID: 1669708, DOI: 10.1111/j.1750-3639.1991.tb00659.x.Peer-Reviewed Original ResearchConceptsNeuronal injuryCentral nervous system manifestationsL-type voltage-dependent calcium channelsVoltage-dependent calcium channelsNervous system manifestationsHIV-1 infectionToxic factorsWhite matter lesionsNeuronal cell deathIntracellular calcium concentrationNeuronal cell typesNeuronal lossSystem manifestationsMatter lesionsEndogenous glutamateImmune cellsGlutamate receptorsGp 120Human neuronsCalcium channelsGp120 fragmentRodent neuronsHIVGp120Potential neurotoxins