2021
A novel gain-of-function sodium channel β2 subunit mutation in idiopathic small fiber neuropathy
Alsaloum M, Labau JIR, Sosniak D, Zhao P, Almomani R, Gerrits M, Hoeijmakers JGJ, Lauria G, Faber CG, Waxman SG, Dib-Hajj S. A novel gain-of-function sodium channel β2 subunit mutation in idiopathic small fiber neuropathy. Journal Of Neurophysiology 2021, 126: 827-839. PMID: 34320850, PMCID: PMC8461825, DOI: 10.1152/jn.00184.2021.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyVoltage-gated sodium channel α-subunitsDorsal root ganglion neuronsSodium channel β subunitsSodium channel α subunitDiscernible causeChannel α-subunitsGanglion neuronsChannel β subunitΒ2 subunitIdiopathic small fiber neuropathySodium currentTetrodotoxin-resistant sodium currentTetrodotoxin-sensitive sodium currentPainful diabetic neuropathySubset of patientsUnmyelinated C-fibersCurrent-clamp analysisAction potential firingHuman pain disordersFirst evidenceNeuropathic painDiabetic neuropathyNeuronal hyperexcitabilityPain disordersPaclitaxel increases axonal localization and vesicular trafficking of Nav1.7
Akin EJ, Alsaloum M, Higerd GP, Liu S, Zhao P, Dib-Hajj FB, Waxman SG, Dib-Hajj SD. Paclitaxel increases axonal localization and vesicular trafficking of Nav1.7. Brain 2021, 144: 1727-1737. PMID: 33734317, PMCID: PMC8320304, DOI: 10.1093/brain/awab113.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsChemotherapy-induced peripheral neuropathyGanglion neuronsSensory axonsNav1.7 channelsPTX treatmentSensory neuronsHuman sensory neuronsEffect of paclitaxelSodium channel Nav1.7Chemotherapy drug paclitaxelAxonal vesicular transportConcentrations of paclitaxelNav1.7 mRNAInflammatory mediatorsNav1.7 expressionPeripheral neuropathyInflammatory milieuPrimary afferentsInflammatory conditionsChannel expressionChannel Nav1.7Nav1.7Increased expressionAxonal localization
2019
Rat NaV1.7 loss-of-function genetic model: Deficient nociceptive and neuropathic pain behavior with retained olfactory function and intra-epidermal nerve fibers
Grubinska B, Chen L, Alsaloum M, Rampal N, Matson D, Yang C, Taborn K, Zhang M, Youngblood B, Liu D, Galbreath E, Allred S, Lepherd M, Ferrando R, Kornecook T, Lehto S, Waxman S, Moyer B, Dib-Hajj S, Gingras J. Rat NaV1.7 loss-of-function genetic model: Deficient nociceptive and neuropathic pain behavior with retained olfactory function and intra-epidermal nerve fibers. Molecular Pain 2019, 15: 1744806919881846. PMID: 31550995, PMCID: PMC6831982, DOI: 10.1177/1744806919881846.Peer-Reviewed Original ResearchConceptsOlfactory functionNav1.7 proteinPain behaviorPain responseRat modelSmall-diameter dorsal root ganglion neuronsNormal intraepidermal nerve fibre densityIntraepidermal nerve fiber densityIntra-epidermal nerve fibersDorsal root ganglion neuronsNeuropathic pain behaviorsNeuropathic pain responsesSpinal nerve ligationNerve fiber densityDorsal root gangliaAction potential firingPeripheral nervous systemEarly postnatal developmentGenetic animal modelsNav1.7 lossNerve ligationPain targetsNeuropathic conditionsGanglion neuronsRoot ganglia
2016
A Molecular Determinant of Subtype-Specific Desensitization in Ionotropic Glutamate Receptors
Alsaloum M, Kazi R, Gan Q, Amin J, Wollmuth LP. A Molecular Determinant of Subtype-Specific Desensitization in Ionotropic Glutamate Receptors. Journal Of Neuroscience 2016, 36: 2617-2622. PMID: 26937003, PMCID: PMC4879209, DOI: 10.1523/jneurosci.2667-15.2016.Peer-Reviewed Original ResearchConceptsIon channelsIonotropic glutamate receptorsHydrophobic boxDiverse animal phylaExtensive sequence alignmentDiverse animal speciesGlutamate-gated ion channelsSingle amino acid differenceExchange mutationAmino acid differencesFast excitatory synaptic transmissionAvailable structural informationAnimal phylaTransmembrane helicesSequence alignmentGlutamate receptorsAcid differencesMolecular determinantsGluN2 subunitsAnimal speciesExtracellular interfaceMotifSynaptic functionReceptor functionNervous system