2022
Inhibition of autophagic flux by S-nitrosylation of SQSTM1/p62 promotes neuronal secretion and cell-to-cell transmission of SNCA/α-synuclein in Parkinson disease and Lewy body dementia
Oh C, Nakamura T, Lipton S. Inhibition of autophagic flux by S-nitrosylation of SQSTM1/p62 promotes neuronal secretion and cell-to-cell transmission of SNCA/α-synuclein in Parkinson disease and Lewy body dementia. Autophagy Reports 2022, 1: 223-225. PMID: 38098743, PMCID: PMC10721282, DOI: 10.1080/27694127.2022.2076770.Peer-Reviewed Original ResearchLewy body dementiaParkinson's diseaseSNCA/α-synucleinAutophagic fluxNitric oxideΑ-synucleinHuman postmortem brainS-nitrosylationNeuronal damageAberrant protein S-nitrosylationSynaptic damageΑ-synucleinopathiesPostmortem brainsPathogenic eventsDiseased brainExcessive reactive oxygenSQSTM1/p62Neurodegenerative disordersInhibits autophagic fluxNeuronal secretionCell-based modelCell transmissionProtein S-nitrosylationDementiaDisease
2007
CHAPTER 25 Functional Characterization of Neurons
McKerchner S, Talantova M, Lipton S. CHAPTER 25 Functional Characterization of Neurons. 2007, 373-386. DOI: 10.1016/b978-012370465-8/50030-2.Peer-Reviewed Original ResearchCentral nervous systemAmyotrophic lateral sclerosisJuvenile-onset diseaseStem cell therapyNeuronal damageCurative treatmentElectrophysiological criteriaMacular degenerationLysosomal storage diseaseParkinson's diseaseLateral sclerosisOnset diseaseNervous systemAlzheimer's diseaseDiseaseCell therapySuch pathologyHuntington's diseaseStorage diseaseEarly childhoodTotal absenceLabeling cellsSclerosisTherapyInjury
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 1InfectionProtection against HIV-1 gp120 and HIV-1 Tat neurotoxicity
Kandanearatchi A, Nath A, Lipton S, Masliah, E, Everall I. Protection against HIV-1 gp120 and HIV-1 Tat neurotoxicity. 2005, 201-210. DOI: 10.1093/oso/9780198526100.003.0019.Peer-Reviewed Original ResearchHIV-1 Tat neurotoxicityViral protein gp120HIV-1 gp120HIV infectionInflammatory changesNeuronal damageTat neurotoxicityPoor prognosisProfound dementiaPathogenetic mechanismsNeurocognitive disordersProtein gp120Cognitive impairmentGp120Mechanisms of toxicityCellular damageNeurotoxicityTranscription (STAT) proteinsHIVPrognosisPathogenesisDementiaInfectionImpairmentBrainExperimental 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
Is tissue plasminogen activator a threat to neurons?
Traynelis S, Lipton S. Is tissue plasminogen activator a threat to neurons? Nature Medicine 2001, 7: 17-18. PMID: 11135603, DOI: 10.1038/83289.Peer-Reviewed Original Research
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 influxTissue plasminogen activator (tPA) increase neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice
Wang Y, Tsirka S, Strickland S, Stieg P, Soriano S, Lipton S. Tissue plasminogen activator (tPA) increase neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nature Medicine 1998, 4: 228-231. PMID: 9461198, DOI: 10.1038/nm0298-228.Peer-Reviewed Original ResearchConceptsTissue plasminogen activatorTPA-deficient miceWild-type miceCerebral infarctsNeuronal damageEffects of tPAIntravenous tissue plasminogen activatorRole of tPAPlasminogen activatorSmall cerebral infarctsAcute cerebral infarctsFocal cerebral ischemiaMiddle cerebral arteryIschemia/reperfusionStroke-induced injuryCerebral viabilityIntravascular filamentAcute strokeExcitotoxic damageCerebral ischemiaCerebral arteryLarge infarctsIntracerebral injectionIntravenous injectionThrombolytic agents
1997
Neurotoxicity associated with dual actions of homocysteine at the N-methyl-d-aspartate receptor
Lipton S, Kim W, Choi Y, Kumar S, D’Emilia D, Rayudu P, Arnelle D, Stamler J. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-d-aspartate receptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 5923-5928. PMID: 9159176, PMCID: PMC20882, DOI: 10.1073/pnas.94.11.5923.Peer-Reviewed Original ResearchMeSH Keywords2-Amino-5-phosphonovalerate6-Cyano-7-nitroquinoxaline-2,3-dioneAdultAnimalsCells, CulturedCerebral CortexChildDizocilpine MaleateEmbryo, MammalianEvoked PotentialsGlycineHomocysteineHumansKineticsKynurenic AcidNeuronsNeurotoxinsN-MethylaspartateRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateConceptsN-methyl-D-aspartate receptorsGlycine coagonist siteHomocysteine neurotoxicityNeuronal damageHead traumaVascular diseaseTotal homocysteineNeurotoxic concentrationsGlycine levelsCoagonist siteNeuroprotective activityCoagulation systemNervous systemDisease pathogenesisPartial antagonistExcessive Ca2HomocysteineAdverse effectsElevated levelsPathological conditionsDual actionVessel wallReceptorsReactive oxygen generationPathogenesis
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 coreAIDS Dementia as a Form of Excitotoxicity: Potential Therapy with NMDA Open-Channel Blockers and Redox Congeners of Nitric Oxide
Lipton S. AIDS Dementia as a Form of Excitotoxicity: Potential Therapy with NMDA Open-Channel Blockers and Redox Congeners of Nitric Oxide. Gwumc Department Of Biochemistry And Molecular Biology Annual Spring Symposia 1996, 341-356. DOI: 10.1007/978-1-4899-0209-2_41.Peer-Reviewed Original ResearchRedox modulatory siteNMDA receptorsOpen channel blockerNeuronal injuryNeuronal damageN-methyl-D-aspartate (NMDA) receptor-operated channelsModulatory siteNMDA open-channel blockersNitric oxideHIV-1 envelope protein gp120Forms of excitotoxicityAIDS dementia complexHIV-1 resultsExcitatory amino acidsMacrophages/microgliaExistence of HIVReceptor-operated channelsFuture pharmacological interventionsFinal common pathwayAmyotrophic lateral sclerosisEnvelope protein gp120Platelet-activating factorReceptor/channel complexNormal neuronal functionNMDA receptor/channel complex
1995
The Coat Protein gp120 of HIV‐1 Inhibits Astrocyte Uptake of Excitatory Amino Acids via Macrophage Arachidonic Acid
Dreyer E, Lipton S. The Coat Protein gp120 of HIV‐1 Inhibits Astrocyte Uptake of Excitatory Amino Acids via Macrophage Arachidonic Acid. European Journal Of Neuroscience 1995, 7: 2502-2507. PMID: 8845955, DOI: 10.1111/j.1460-9568.1995.tb01048.x.Peer-Reviewed Original ResearchConceptsExcitatory amino acidsAmino acidsAstrocyte uptakeNeuronal damageProtein gp120Excitatory amino acid uptakeAmino acid uptakeN-methyl-D-aspartate receptorsArachidonic acidCentral mammalian neuronsMammalian neuronsReleases arachidonic acidNeuronal injuryBrain macrophagesImmunodeficiency syndromeNeurological dysfunctionAcid uptakeExcess glutamateGp120MacrophagesAstrocytesNeuronsInitial activationPresent dataUptake
1994
The 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 disease
1992
Blockade of NMDA receptor-mediated mobilization of intracellular Ca2+ prevents neurotoxicity
Lei S, Zhang D, Abele A, Lipton S. Blockade of NMDA receptor-mediated mobilization of intracellular Ca2+ prevents neurotoxicity. Brain Research 1992, 598: 196-202. PMID: 1486480, DOI: 10.1016/0006-8993(92)90183-a.Peer-Reviewed Original ResearchConceptsIntracellular Ca2Extracellular Ca2Excessive NMDA receptor stimulationRetinal ganglion cell neuronsNMDA receptor-mediated neurotoxicityGanglion cell neuronsNMDA receptor activationReceptor-mediated mobilizationNMDA receptor stimulationNormal extracellular Ca2Neuronal damagePharmacological interventionsPrevents neurotoxicityReceptor stimulationPresence of EGTAIntracellular storesNMDACell neuronsReceptor activationCultured ratDelayed neurotoxicityDantroleneNeurotoxicityElevated Ca2NeuronsMemantine prevents HIV coat protein-induced neuronal injury in vitro.
Lipton S. Memantine prevents HIV coat protein-induced neuronal injury in vitro. Neurology 1992, 42: 1403-5. PMID: 1620355, DOI: 10.1212/wnl.42.7.1403.Peer-Reviewed Original ResearchConceptsNeuronal injuryNeuronal damageHIV-1 coat protein gp120Cognitive/motor complexRat retinal ganglion cellsN-methyl-D-aspartate receptorsHuman immunodeficiency virusPossible protective effectNMDA receptor-operated ion channelsRetinal ganglion cellsReceptor-operated ion channelsMicroM memantineNeurologic deficitsImmunodeficiency virusGanglion cellsNMDA antagonistsProtective effectProtein gp120Therapeutic potentialGp120InjuryMemantineMotor complexConcurrent activationIon channelsModels of neuronal injury in AIDS: another role for the NMDA receptor?
Lipton S. Models of neuronal injury in AIDS: another role for the NMDA receptor? Trends In Neurosciences 1992, 15: 75-79. PMID: 1373919, DOI: 10.1016/0166-2236(92)90013-x.Peer-Reviewed Original ResearchConceptsNMDA receptor-operated channelsExistence of HIVVoltage-dependent Ca2Receptor-operated channelsFuture pharmacological interventionsFinal common pathwayDysfunction of cognitionDemise of neuronsNeuronal injuryNeurological manifestationsNeuronal damageImmunodeficiency syndromeAIDS patientsNMDA receptorsNeuronal susceptibilityPharmacological interventionsType 1 resultsCommon pathwayNeuronsPatientsInjuryTwo-thirdsHIVDysfunctionEpilepsy
1991
Synergistic effects of HIV coat protein and NMDA receptor-mediated neurotoxicity
Lipton S, Sucher N, Kaiser P, Dreyer E. Synergistic effects of HIV coat protein and NMDA receptor-mediated neurotoxicity. Neuron 1991, 7: 111-118. PMID: 1676893, DOI: 10.1016/0896-6273(91)90079-f.Peer-Reviewed Original ResearchConceptsNMDA receptor-mediated neurotoxicityHIV-1 coat protein gp120Whole-cell patch-clamp recordingsHIV coat proteinRat retinal culturesSubsequent neuronal damagePatch-clamp recordingsGlutamate pyruvate transaminaseNeuronal injuryNeuronal damageEndogenous glutamateGanglion cellsNMDA antagonistsProtein gp120Low picomolar concentrationsRetinal culturesGp120NeurotoxicityComplete protectionMinute increasePicomolar concentrationsGlutamateInjuryAntagonistTransaminaseCalcium 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 concentrationsGp120