2024
Disordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders
Dib-Hajj S, Waxman S. Disordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders. Journal Of Clinical Investigation 2024, 134: e182198. PMID: 38949022, PMCID: PMC11213459, DOI: 10.1172/jci182198.Peer-Reviewed Original ResearchConceptsTetrodotoxin-sensitiveHyperexcitability disordersSensory neuronsExcitability of sensory neuronsGene therapy modalitiesPeripheral sensory neuronsVoltage-gated sodiumMinimal side effectsGene therapyInduce analgesiaTherapy modalitiesSide effectsTherapeutic strategiesNav channelsAttenuating excitationIn vivoHyperexcitabilityAnalgesiaNeuronsDisordersPainTherapyGenesBiodistributionRats
2020
Cumulative hydropathic topology of a voltage‐gated sodium channel at atomic resolution
Xenakis M, Kapetis D, Yang Y, Heijman J, Waxman S, Lauria G, Faber C, Smeets H, Westra R, Lindsey P. Cumulative hydropathic topology of a voltage‐gated sodium channel at atomic resolution. Proteins Structure Function And Bioinformatics 2020, 88: 1319-1328. PMID: 32447794, DOI: 10.1002/prot.25951.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceArcobacterBacterial ProteinsBinding SitesHydrophobic and Hydrophilic InteractionsIon Channel GatingModels, MolecularProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsSodiumThermodynamicsVoltage-Gated Sodium ChannelsConceptsVoltage-gated sodium channelsBacterial channelsPhysiological cellular activitySodium channelsCellular activitiesCell membraneBiological poresPore stabilityAtomic resolutionBiophysical significanceMembrane surfaceHydropathicityGenesProteinMutationsWide spectrumMembraneFunctional architectureAccumulationComputational frameworkSodium ionsPores
2006
Transcriptional Channelopathies of the Nervous System
Waxman S. Transcriptional Channelopathies of the Nervous System. 2006 DOI: 10.1002/9780470015902.a0006086.Peer-Reviewed Original ResearchSodium channel geneChannel genesTranscriptional channelopathiesSodium channel gene expressionChannel gene expressionGene expressionPeripheral nerve injurySpinal sensory neuronsGenesDysregulated expressionNerve injuryMultiple sclerosisSensory neuronsNervous systemCerebellar functionRecent studiesExpressionChannelopathiesAbstract Recent studiesHyperexcitabilitySclerosisInjuryNeuronsCells
2005
Chapter 19 Transcriptional Channelopathies of the Nervous System New Targets for Molecular Medicine
Waxman S. Chapter 19 Transcriptional Channelopathies of the Nervous System New Targets for Molecular Medicine. 2005, 319-338. DOI: 10.1016/b978-012738903-5/50020-5.Peer-Reviewed Original ResearchTranscriptional channelopathiesIon channel genesChannel genesUnique amino acid sequenceAmino acid sequenceVoltage-gated sodium channelsGene productsAcid sequenceNew therapeutic opportunitiesProtein structureGenesTranscriptionNeuronal functionMolecular targetsMolecular medicineChannel transcriptionNew targetsNew therapeutic strategiesTherapeutic opportunitiesSodium channelsSpecific targetingComplete understandingChannelopathiesTherapeutic strategiesNervous system
2000
Sodium channels and their genes: dynamic expression in the normal nervous system, dysregulation in disease states11Published on the World Wide Web on 15 August 2000.
Waxman S, Dib-Hajj S, Cummins T, Black J. Sodium channels and their genes: dynamic expression in the normal nervous system, dysregulation in disease states11Published on the World Wide Web on 15 August 2000. Brain Research 2000, 886: 5-14. PMID: 11119683, DOI: 10.1016/s0006-8993(00)02774-8.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSodium channel gene expressionSodium channel geneChannel gene expressionChannel genesGene expressionPost-transcriptional levelNormal nervous systemSodium channel expressionSodium channelsChannel expressionMolecular plasticityGenesDynamic expressionCell membraneHypothalamic magnocellular neurosecretory neuronsDifferent repertoiresMultiple sclerosisNervous systemTherapeutic opportunitiesSodium channel subtypesExpressionElectrogenic propertiesRegulationChannel subtypesDysregulationThe neuron as a dynamic electrogenic machine: modulation of sodiumchannel expression as a basis for functional plasticity in neurons
Waxman S. The neuron as a dynamic electrogenic machine: modulation of sodiumchannel expression as a basis for functional plasticity in neurons. Philosophical Transactions Of The Royal Society B Biological Sciences 2000, 355: 199-213. PMID: 10724456, PMCID: PMC1692729, DOI: 10.1098/rstb.2000.0559.Peer-Reviewed Original ResearchConceptsSodium channelsMammalian nervous systemSodium channel geneNervous systemDozen genesDistinct sodium channelsVoltage-gated sodium channelsGenesElectrogenic machineryNormal nervous systemSodium channel expressionFunctional plasticityMembrane of neuronsAction potential activityTranscriptionPathological insultsPhysiological inputsMost neuronsCrucial roleExpressionNeuronsFunctional propertiesElectroresponsive propertiesPotential activityMachinery
1999
Coding Sequence, Genomic Organization, and Conserved Chromosomal Localization of the Mouse Gene Scn11a Encoding the Sodium Channel NaN
Dib-Hajj S, Tyrrell L, Escayg A, Wood P, Meisler M, Waxman S. Coding Sequence, Genomic Organization, and Conserved Chromosomal Localization of the Mouse Gene Scn11a Encoding the Sodium Channel NaN. Genomics 1999, 59: 309-318. PMID: 10444332, DOI: 10.1006/geno.1999.5890.Peer-Reviewed Original ResearchConceptsSodium channel geneChannel genesConserved linkage groupMouse chromosome 9Sodium channel alphaAlternative exon 5Amino acid levelsGenomic organizationChromosomal localizationLinkage groupsHuman genesHuman SCN5ACoding sequenceCommon lineageChannel alphaChromosome 9TTX-R sodium channelsGenesSmall-diameter sensory neuronsTransduction of painDorsal root gangliaHigh-threshold nociceptorsExon 5SCN11A geneSodium channelsActivation and Inactivation of the Voltage-Gated Sodium Channel: Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation
Bendahhou S, Cummins T, Tawil R, Waxman S, Ptácek L. Activation and Inactivation of the Voltage-Gated Sodium Channel: Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation. Journal Of Neuroscience 1999, 19: 4762-4771. PMID: 10366610, PMCID: PMC6782655, DOI: 10.1523/jneurosci.19-12-04762.1999.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDNA Mutational AnalysisDNA PrimersGene ExpressionHumansHyperkalemiaIon Channel GatingKidneyKineticsMaleMiddle AgedMolecular Sequence DataNAV1.4 Voltage-Gated Sodium ChannelParalyses, Familial PeriodicPatch-Clamp TechniquesPoint MutationProtein Structure, TertiarySequence Homology, Amino AcidSodium ChannelsTransfectionConceptsSegments S5Point mutationsS5 segmentVoltage-Gated Sodium ChannelSodium channelsTransmembrane segments S5Cytoplasmic interfaceWild-type channelsParalysis phenotypeHomologous domainsVoltage-sensitive sodium channelsPotassium-aggravated myotoniaNew point mutationPhenylalanine substitutionSkeletal muscle disordersHyperkalaemic periodic paralysisFast inactivationSecond domainMutationsGenesChannel deactivationInactivationChannel activationSlow inactivationT704M mutation