2023
Senataxin helicase, the causal gene defect in ALS4, is a significant modifier of C9orf72 ALS G4C2 and arginine-containing dipeptide repeat toxicity
Bennett C, Dastidar S, Arnold F, McKinstry S, Stockford C, Freibaum B, Sopher B, Wu M, Seidner G, Joiner W, Taylor J, West R, La Spada A. Senataxin helicase, the causal gene defect in ALS4, is a significant modifier of C9orf72 ALS G4C2 and arginine-containing dipeptide repeat toxicity. Acta Neuropathologica Communications 2023, 11: 164. PMID: 37845749, PMCID: PMC10580588, DOI: 10.1186/s40478-023-01665-z.Peer-Reviewed Original ResearchConceptsDipeptide repeatsFamilial amyotrophic lateral sclerosisAmyotrophic lateral sclerosisRNA-protein interactionsC9orf72 amyotrophic lateral sclerosisMobility of proteinsNuclear helicaseRNA-dependentDrosophila modelFly linesSenataxin functionFly modelCellular processesC9orf72 geneMembraneless organellesGenetic modifiersSenataxinMovement assayGenetic causeCo-expressionPrimary neuronsDisease phenotypeSporadic amyotrophic lateral sclerosisAge-related motor deficitsHEK293 cellsReduction of Nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43-related neurodegeneration
Tejwani L, Jung Y, Kokubu H, Sowmithra S, Ni L, Lee C, Sanders B, Lee P, Xiang Y, Luttik K, Soriano A, Yoon J, Park J, Ro H, Ju H, Liao C, Tieze S, Rigo F, Jafar-Nejad P, Lim J. Reduction of Nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43-related neurodegeneration. Journal Of Clinical Investigation 2023, 133: e138207. PMID: 37384409, PMCID: PMC10425213, DOI: 10.1172/jci138207.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisTDP-43-related neurodegenerationNeurodegenerative disordersTransactive response DNA-binding protein 43Sporadic amyotrophic lateral sclerosisDNA-binding protein 43Subset of patientsTDP-43 speciesTDP-43 inclusionsDistinct mouse modelsTDP-43 proteinopathyFamilial amyotrophic lateral sclerosisNemo-like kinaseMultiple neurodegenerative disordersAutophagy/lysosome pathwayTDP-43-positive aggregatesALS patientsALS casesSporadic ALSPharmacological reductionProtein 43Lateral sclerosisMouse modelParkinson's diseaseTDP-43
2022
piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis
Abdelhamid R, Ogawa K, Beck G, Ikenaka K, Takeuchi E, Yasumizu Y, Jinno J, Kimura Y, Baba K, Nagai Y, Okada Y, Saito Y, Murayama S, Mochizuki H, Nagano S. piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis. Molecular Neurobiology 2022, 59: 1693-1705. PMID: 35015250, PMCID: PMC8882100, DOI: 10.1007/s12035-021-02686-2.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsNon-coding RNAsBind to PIWI-interacting RNAsDysregulation of piRNAsControl postmortem brain samplesAmyotrophic lateral sclerosisTDP-43Biogenesis of RNAsAggregation of TAR DNA-binding protein 43RNA-binding proteinsTAR DNA-binding protein 43DNA-binding protein 43Abnormal RNA metabolismNcRNA biogenesisPIWI proteinsPiwi homologsSilencing 1Sporadic ALSRNA metabolismRNA-seqTDP-43 pathologyProtein complexesPIWIL1Sporadic amyotrophic lateral sclerosisPathological hallmark
2020
Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial
Weiss M, Macklin E, McIlduff C, Vucic S, Wainger B, Kiernan M, Goutman S, Goyal N, Rutkove S, Ladha S, Chen I, Harms M, Brannagan T, Lacomis D, Zivkovic S, Ma M, Wang L, Simmons Z, Rivner M, Shefner J, Cudkowicz M, Atassi N, Group F. Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial. Muscle & Nerve 2020, 63: 371-383. PMID: 33340120, PMCID: PMC8513796, DOI: 10.1002/mus.27146.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAmyotrophic Lateral SclerosisAxonsCortical ExcitabilityDouble-Blind MethodElectrodiagnosisElectromyographyEvoked Potentials, MotorFemaleHumansMaleMedian NerveMexiletineMiddle AgedNeural ConductionPreliminary DataTranscranial Magnetic StimulationVoltage-Gated Sodium Channel BlockersConceptsEffects of mexiletineResting motor thresholdSporadic amyotrophic lateral sclerosisRandomized Controlled TrialsAxonal hyperexcitabilityAmyotrophic lateral sclerosisRandomized to placeboAxonal excitability studiesCompared to placeboPhase II randomized controlled trialSecondary outcome measuresTranscranial magnetic stimulationPrimary endpointLateral sclerosisAxonal excitabilityHalf-timeTreated subjectsMexiletineReduction of motorControlled TrialsHyperexcitabilityALS subjectsAlternative causesMagnetic stimulationOutcome measures
2017
Clinical and neuropathological features of ALS/FTD with TIA1 mutations
Hirsch-Reinshagen V, Pottier C, Nicholson A, Baker M, Hsiung G, Krieger C, Sengdy P, Boylan K, Dickson D, Mesulam M, Weintraub S, Bigio E, Zinman L, Keith J, Rogaeva E, Zivkovic S, Lacomis D, Taylor J, Rademakers R, Mackenzie I. Clinical and neuropathological features of ALS/FTD with TIA1 mutations. Acta Neuropathologica Communications 2017, 5: 96. PMID: 29216908, PMCID: PMC5719900, DOI: 10.1186/s40478-017-0493-x.Peer-Reviewed Original ResearchConceptsT-cell-restricted intracellular antigen 1Frontotemporal dementiaTDP-43TDP-43 pathologyAmyotrophic lateral sclerosisLanguage impairmentMotor neuronsPattern of neurodegenerationPsychiatric featuresSporadic ALSFrontotemporal lobar degenerationPyramidal motor systemTDP-43 proteinopathyDiagnosis of amyotrophic lateral sclerosisSporadic amyotrophic lateral sclerosisCaudate atrophyFeatures of amyotrophic lateral sclerosisRepeat expansionRestriction patternsInitial presentationMotor systemMutation carriersFocal weaknessDisease durationClinical phenotype
2012
Hexanucleotide repeat expansions in C9ORF72 in the spectrum of motor neuron diseases
van Rheenen W, van Blitterswijk M, Huisman M, Vlam L, van Doormaal P, Seelen M, Medic J, Dooijes D, de Visser M, van der Kooi A, Raaphorst J, Schelhaas H, van der Pol W, Veldink J, van den Berg L, Weiner M, Aisen P, Petersen R, Clifford R, Jagust W, Trojanowki J, Toga A, Beckett L, Green R, Saykin A, Morris J, Liu E, Montine T, Gamst A, Thomas R, Donohue M, Walter S, Gessert D, Sather T, Beckett L, Harvey D, Gamst A, Donohue M, Kornak J, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Bandy D, Koeppe R, Foster N, Reiman E, Chen K, Mathis C, Cairns N, Taylor-Reinwald L, Shaw L, Lee V, Korecka M, Crawford K, Neu S, Foroud T, Potkin S, Shen L, Kachaturian Z, Frank R, Snyder P, Kaye J, Dolen S, Quinn J, Schneider L, Pawluczyk S, Spann B, Brewer J, Vanderswag H, Heidebrink J, Lord J, Petersen R, Johnson K, S. Doody R, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig L, Bell K, Morris J, Mintun M, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Mitsis E, Romirowsky A, deToledo-Morrell L, Shah R, Duara R, Varon D, Roberts P, Albert M, Onyike C, Kielb S, Rusinek H, de Leon M, Glodzik L, Doraiswamy P, Petrella J, Arnold S, Karlawish J, Wolk D, Smith C, Jicha G, Hardy P, Lopez O, Oakley M, Simpson D, Ismail M, Brand C, Mulnard R, Thai G, Mc-Adams-Ortiz C, Diaz-Arrastia R, Martin-Cook K, DeVous M, Levey A, Lah J, Cellar J, Burns J, Anderson H, Swerdlow R, Bartzokis G, Silverman D, Lu P, Apostolova L, Graff-Radford N, Parfitt F, Johnson H, Farlow M, Herring S, Hake A, van Dyck C, Carson R, MacAvoy M, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Hsiung G, Feldman H, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Wu C, Johnson N, Mesulam M, Sadowsky C, Martinez W, Villena T, Turner R, Johnson K, Reynolds B, Sperling R, Frey M, Johnson K, Rosen A, Tinklenberg J, Sabbagh M, Belden C, Jacobson S, Killiany R, Norbash A, Obisesan T, Wolday S, Bwayo S, Lerner A, Hudson L, Ogrocki P, DeCarli C, Fletcher E, Carmichael O, Kittur S, Borrie M, Lee T, Bartha R, Johnson S, Asthana S, Carlsson C, Potkin S, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Hendin B, Scharre D, Kataki M, Zimmerman E, Celmins D, Brown A, Pearlson G, Blank K, Anderson K, Saykin A, Santulli R, Schwartz E, Williamson J, Sink K, Watkins F, Ott B, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen H, Miller B, Mintzer J, Longmire C, Spicer K, Kwon S, Kim J, Cho K, Shin D, Ko Y, Lee S, Cha J, Kim Y, Shin D, Jang H, Choi N, Hong S, Rha J, Hong K, Kim E, Choi J, Sohn S, Shin W, HyukHeo S, Chung K, Park J, Lee J, Park J, Park T, Bae H, Han M, Kwon H, Lee K, Lee T, Jeong D, Lee J, Ashwal S, deVeber G, Ferriero D, Fullerton H, Ichord R, Kirkham F, Lynch J, O'Callaghan F, Pavlakis S, Sebire G, Willan A, Willan A, Sofronas M, Dlamini N, Elbers J, Nowak-Göttl U, Düring C, Krümpel A, Plumb P, Journeycake J, van de Bruinhorst K, Gossett D, Hernandez Chavez M, Monagle P, MacKay M, Barnes C, Furmedge J, Gordon A, Benedict S, Bale J, Nielson D, Abdalla A, Chadehumbe M, Kabbouche M, Karti P, Phillips T, Friedman N, Rizkallah E, Zamel K, Wiznitzer M, Lidsky K, Bernard T, Goldenberg N, Armstrong-Wells J, Booth F, Nash M, Beslow L, Carpenter J, Chang T, Weinstein S, Kan L, Smith R, Maytal J, Sy-Kho R, Yager J, Massicotte P, Ashwal S, McClure C, Bjornson B, Hukin J, Bucevska M, Kent S, Riviello J, Rivkin M, Trenor C, Amlie-Lefond C, Whelan H, Ferriero D, Fullerton H, Fox C, Pavlakis S, Goodman S, Levinson K, Kolk A, Laugesaar R, Talvik T, Imam H, Thomas T, Golomb M, Kirton A, Heyer G, Ganesan V, Saengpattrachai M, Crosswell H, Mancuso A, Tatishvili N, Yeh A, Humpherys P, Abraham L, Alveal L, Ortiz M, Altuna D, Maxit C, Gonzalez V, Alam M, Buckley D, Penney S, Jordan L, Grabowski E, Chan A, Deray M, Khatib Z, Kovacevic G, Kosofsky B, Leifer D, Nass R, Wong V, Catsman C, El-Hakam L, Sebire G, Cholette J, Narang S, Lerner N, Carpenter S, Bischoff K, Frei-Jones M, Masur D, Epstein L, Bagiella E, Hinton V, Gallentine W, Rende E, Provenzale J, Voyvodic J, Song A, Conklin T, O'Hara K, Seinfeld S, Conry J, Glauser T, Ayala J, Facchini R, Sigalova M, Hannigan J, Weiss E, Mancini A, Curran J, Ahlm S, Renaldi J, Umanzour D, Kim A, Hamidullah A, Litherland C, Bonner M, Xu Y, Van de Water V, Grasso S, Kushner D, Culbert J, Bush B, Chandrasekaran S, Davis L, Rogers C, Sabo C, Wang H, Noebels J. Hexanucleotide repeat expansions in C9ORF72 in the spectrum of motor neuron diseases. Neurology 2012, 79: 878-882. PMID: 22843265, DOI: 10.1212/wnl.0b013e3182661d14.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge of OnsetAgedAged, 80 and overAmyotrophic Lateral SclerosisC9orf72 ProteinCohort StudiesConfidence IntervalsDementiaDNADNA Repeat ExpansionFemaleFrontotemporal Lobar DegenerationGenotypeHumansMaleMiddle AgedMotor Neuron DiseaseMuscular Atrophy, SpinalMutationParkinson DiseasePolymerase Chain ReactionProportional Hazards ModelsProteinsSurvivalYoung AdultConceptsProgressive muscular atrophyPrimary lateral sclerosisAmyotrophic lateral sclerosisSporadic amyotrophic lateral sclerosisParkinson's diseaseShorter survivalLateral sclerosisRelatives of patientsFamilial aggregationRepeat expansionHexanucleotide repeat expansionControl subjectsMotor neuronsLarge cohortPatientsMuscular atrophyGenetic testingEarly onsetMajor causeDementiaC9orf72SclerosisFALSEarly ageDutch descent
2007
Motoneuron-specific NR3B gene: No association with ALS and evidence for a common null alleleSYMBOL
Niemann S, Landers J, Churchill M, Hosler B, Sapp P, Speed W, Lahn B, Kidd K, Brown R, Hayashi Y. Motoneuron-specific NR3B gene: No association with ALS and evidence for a common null alleleSYMBOL. Neurology 2007, 70: 666-676. PMID: 17687115, DOI: 10.1212/01.wnl.0000271078.51280.17.Peer-Reviewed Original ResearchMeSH KeywordsAllelesCase-Control StudiesDNA Mutational AnalysisGene FrequencyGenetic Predisposition to DiseaseGenetics, PopulationGenotypeHaplotypesHumansLinkage DisequilibriumMotor Neuron DiseaseMotor NeuronsPolymorphism, Single NucleotideReceptors, N-Methyl-D-AspartateSuperoxide DismutaseSuperoxide Dismutase-1ConceptsSporadic amyotrophic lateral sclerosisAmyotrophic lateral sclerosisSingle nucleotide polymorphismsGRIN3B geneGlutamate-mediated excitotoxicityCase-control studyFamilial amyotrophic lateral sclerosisIonotropic glutamate receptorsNervous system-related genesTag single nucleotide polymorphismsPolymorphic CAG repeatNMDA typeGlutamate receptorsLateral sclerosisReceptor responsesAllele frequenciesCommon polymorphismsUnreported single nucleotide polymorphismsNR3BCAG repeatsGenetic dysfunctionGRIN3BNucleotide polymorphismsNull allelesIndividuals
1998
Advanced Glycation Endproducts in Neurofilament Conglomeration of Motoneurons in Familial and Sporadic Amyotrophic Lateral Sclerosis
Chou S, Wang H, Taniguchi A, Bucala R. Advanced Glycation Endproducts in Neurofilament Conglomeration of Motoneurons in Familial and Sporadic Amyotrophic Lateral Sclerosis. Molecular Medicine 1998, 4: 324-332. PMID: 9642682, PMCID: PMC2230387, DOI: 10.1007/bf03401739.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisSporadic amyotrophic lateral sclerosisNeurofilament proteinNeuronal inclusionsLateral sclerosisAGE formationNitric oxide-mediated responsesAnti-AGE antibodyAdvanced glycation endproductsMethodsParaffin sectionsMotor neuronsConclusionsThese dataAdvanced glycationGlycation endproductsNeuronal toxicityNitric oxideSpecific antibodiesProtein nitrationConcomitant inductionSclerosisSuperoxide dismutasePatientsAntibodiesPotent oxidantFree radicals
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