2021
Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases
Trudler D, Ghatak S, Lipton S. Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases. International Journal Of Molecular Sciences 2021, 22: 8196. PMID: 34360966, PMCID: PMC8347370, DOI: 10.3390/ijms22158196.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseDrug DiscoveryHumansInduced Pluripotent Stem CellsNeuroprotective AgentsPrecision MedicineConceptsAmyotrophic lateral sclerosisNeurodegenerative diseasesParkinson's diseaseAnimal modelsAlzheimer's diseaseEffective disease-modifying therapiesHuntington's diseaseDisease-modifying therapiesSeverity of symptomsHuman samplesHiPSC-derived neural cellsHealthy donorsEffective treatmentLateral sclerosisEconomic burdenHuman-induced pluripotent stem cell (hiPSC) technologyProgressive deteriorationNeural functionDiseaseHiPSC modelsNeural cellsPluripotent stem cell (iPSC) technologyDisease mechanismsPoor accessMillions of people
2006
Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophillic phase II inducers
Satoh T, Okamoto S, Cui J, Watanabe Y, Furuta K, Suzuki M, Tohyama K, Lipton S. Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophillic phase II inducers. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 768-773. PMID: 16407140, PMCID: PMC1334635, DOI: 10.1073/pnas.0505723102.Peer-Reviewed Original ResearchConceptsNeurite outgrowth-promoting prostaglandinsHemeoxygenase-1Cerebral ischemia/reperfusion injuryKeap1/Nrf2/HOIschemia/reperfusion injuryGlutamate-related excitotoxicityKeap1/Nrf2 pathwayNrf2/HOHO-1 expressionCultured neuronal cellsInactivation of Nrf2Phase II enzymesThiol-dependent mannerTranscription factor Nrf2HO-1 promoterNeuroprotective actionReperfusion injuryNeuroprotective compoundsNrf2 pathwayTherapeutic approachesNrf2 translocationAntioxidant responsive elementNeurodegenerative disordersNeuronal cellsFactor Nrf2
2005
Experimental 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 ResearchMeSH KeywordsAIDS Dementia ComplexAnimalsHIV-1HumansNeuroprotective AgentsNeurotoxinsReceptors, ChemokineReceptors, ErythropoietinReceptors, GlutamateConceptsHuman 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
2003
Paradigm shift in neuroprotective drug development: clinically tolerated NMDA receptor inhibition by memantine
Lipton S, Chen H. Paradigm shift in neuroprotective drug development: clinically tolerated NMDA receptor inhibition by memantine. Cell Death & Differentiation 2003, 11: 18-20. PMID: 14647237, DOI: 10.1038/sj.cdd.4401344.Peer-Reviewed Original Research
2001
Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-κB signalling cascades
Digicaylioglu M, Lipton S. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-κB signalling cascades. Nature 2001, 412: 641-647. PMID: 11493922, DOI: 10.1038/35088074.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell NucleusCells, CulturedDNAErythropoietinGenes, ReporterJanus Kinase 2NeuronsNeuroprotective AgentsNF-kappa BNitric OxideN-MethylaspartateProtein BindingProtein TransportProtein-Tyrosine KinasesProto-Oncogene ProteinsRatsReceptors, ErythropoietinSignal TransductionSuperoxide DismutaseTumor Necrosis Factor-alphaConceptsHypoxia-inducible factor-1EPO receptorForm of JAK2Transcription factor hypoxia-inducible factor-1NF-κB-dependent transcriptionNF-κB functionActivation of JAK2Subsequent nuclear translocationTranscription factor NF-κBNF-κBFactor NF-κBSignaling cascadesNitric oxideKinase 2NF-κB signaling cascadesHypoxic-ischemic preconditioningNuclear translocationNeuroprotective genesFactor 1JAK2Neuroprotective pathwaysNeuronal apoptosisCerebrocortical neuronsEPO effectsDegenerative damageChapter 51 Retinal ganglion cells, glaucoma and neuroprotection
Lipton S. Chapter 51 Retinal ganglion cells, glaucoma and neuroprotection. Progress In Brain Research 2001, 131: 713-718. PMID: 11420983, DOI: 10.1016/s0079-6123(01)31055-5.Peer-Reviewed Original Research
2000
Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury
Li M, Ona V, Chen M, Kaul M, Tenneti L, Zhang X, Stieg P, Lipton S, Friedlander R. Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury. Neuroscience 2000, 99: 333-342. PMID: 10938439, DOI: 10.1016/s0306-4522(00)00173-1.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCord injuryCaspase-1Acute central nervous system insultLesion sizeCentral nervous system insultsTraumatic spinal cord injuryVehicle-treated miceSham-operated miceNervous system insultsCaspase-3Spinal cord samplesNon-neuronal cellsN-benzyloxycarbonyl-ValCaspase-1 activityCaspase-3 expressionCell deathNeurological dysfunctionCord samplesMotor functionTissue injuryMouse modelTherapeutic implicationsTransgenic miceTissue damageRole of p38 Mitogen-Activated Protein Kinase in Axotomy-Induced Apoptosis of Rat Retinal Ganglion Cells
Kikuchi M, Tenneti L, Lipton S. Role of p38 Mitogen-Activated Protein Kinase in Axotomy-Induced Apoptosis of Rat Retinal Ganglion Cells. Journal Of Neuroscience 2000, 20: 5037-5044. PMID: 10864961, PMCID: PMC6772303, DOI: 10.1523/jneurosci.20-13-05037.2000.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAxonal TransportAxotomyCell NucleusCell SurvivalDizocilpine MaleateEnzyme InhibitorsFluorescent DyesImidazolesKineticsMaleMitogen-Activated Protein KinasesNeuroprotective AgentsOptic NerveP38 Mitogen-Activated Protein KinasesPhosphorylationPyridinesRatsRats, Long-EvansRetinal Ganglion CellsSignal TransductionStilbamidinesTime FactorsConceptsRetinal ganglion cellsProtein kinaseP38 Mitogen-Activated Protein KinaseMitogen-Activated Protein KinaseMAP kinase activationIntracellular signal transductionRole of p38P38 MAP kinase activationApoptotic cell deathDose-dependent mannerP38 MAP kinase inhibitorMAP kinase inhibitorRGC apoptosisOptic nerveGanglion cellsSignal transductionNMDA receptorsAxotomy-induced apoptosisApoptotic signalingKinase activationP38 inhibitorRat retinal ganglion cellsCell deathCell typesOptic nerve trauma
1999
Neuroprotection by the NMDA receptor-associated open-channel blocker memantine in a photothrombotic model of cerebral focal ischemia in neonatal rat
Stieg P, Sathi S, Warach S, Le D, Lipton S. Neuroprotection by the NMDA receptor-associated open-channel blocker memantine in a photothrombotic model of cerebral focal ischemia in neonatal rat. European Journal Of Pharmacology 1999, 375: 115-120. PMID: 10443569, DOI: 10.1016/s0014-2999(99)00214-9.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingSide effectsInfarct sizeNeonatal ratsChannel blockersNMDA receptorsFocal cerebral ischemia modelNeurobehavioral side effectsIschemic brain injuryEffects of memantineExcitatory amino acidsInduction of strokeRodent stroke modelsAdult animal modelsCerebral ischemia modelSubstantial side effectsCerebral focal ischemiaNumerous side effectsNeuronal cell culturesNeonatal neuronsPhotochemical thrombosisPhotothrombotic modelNeuronal injuryCerebral ischemiaFocal ischemia
1998
Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation
Chen H, Wang Y, Rayudu P, Edgecomb P, Neill J, Segal M, Lipton S, Jensen F. Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation. Neuroscience 1998, 86: 1121-1132. PMID: 9697119, DOI: 10.1016/s0306-4522(98)00163-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody TemperatureBrain IschemiaCytoplasmExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsIn Vitro TechniquesLong-Term PotentiationMaleMaze LearningMemantineMicroscopy, ElectronNeuronsNeuroprotective AgentsRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateVacuolesConceptsN-methyl-D-aspartate antagonistsLong-term potentiationAspartate antagonistDizocilpine maleateSide effectsUncompetitive N-methyl-D-aspartate antagonistsN-methyl-D-aspartate blockersMorris water maze performancePost-ischemic administrationHypoxia/ischemiaExcitatory postsynaptic currentsN-methyl-D-aspartate (NMDA) channelsAdverse side effectsWater maze performanceHuman CNS disordersExcitotoxic disordersNeuroprotective concentrationsClinical tolerabilityNeuroprotective dosesClinical efficacyInfarct sizePostsynaptic currentsHippocampal slicesCNS disordersAdult ratsChapter 6 Redox modulation of the NMDA receptor by NO-related species
Lipton S, Rayudu P, Choi Y, Sucher N, Chen H. Chapter 6 Redox modulation of the NMDA receptor by NO-related species. Progress In Brain Research 1998, 118: 73-82. PMID: 9932435, DOI: 10.1016/s0079-6123(08)63201-x.Peer-Reviewed Original ResearchConceptsChemical reactionsMechanism of reactionRedox stateReactive thiol groupsCatalytic amountFurther oxidationThiol groupsElectron acceptorPreferred reactionReceptor sulfhydryl groupsChemical evidenceSinglet stateNO groupBiological activityMolecular switchReactionThiolsDisulfide bondsSulfhydryl groupsCritical thiolsO2NOS-nitrosylationRedox modulationBondsNeuroprotective versus neurodestructive effects of NO‐related species
Lipton S, Choi Y, Sucher N, Chen H. Neuroprotective versus neurodestructive effects of NO‐related species. BioFactors 1998, 8: 33-40. PMID: 9699006, DOI: 10.1002/biof.5520080107.Peer-Reviewed Original ResearchConceptsNMDA receptorsCentral nervous systemNMDA receptor subunitsNeuronal injuryNeurodestructive effectsNervous systemRedox modulationReceptor subunitsNitric oxideExcessive Ca2Protective actionChannel activitySuperoxide anionNO groupReceptorsS-nitrosylationGroupDiverse tissuesNeuroprotectionInjuryBrain