2023
Dysregulation of alternative splicing in spinocerebellar ataxia type 1
Olmos V, Thompson E, Gogia N, Luttik K, Veeranki V, Ni L, Sim S, Chen K, Krause D, Lim J. Dysregulation of alternative splicing in spinocerebellar ataxia type 1. Human Molecular Genetics 2023, 33: 138-149. PMID: 37802886, PMCID: PMC10979408, DOI: 10.1093/hmg/ddad170.Peer-Reviewed Original ResearchConceptsAlternative splicing eventsSpinocerebellar ataxia type 1Splicing eventsAtaxin-1Ataxia type 1Mutant ataxin-1Alternative splicingGene expressionMisregulated alternative splicingCell-autonomous mannerDifferential gene expressionNew biological pathwaysMolecular mechanistic insightsDrosophila modelGenetic manipulationBulk RNABiological pathwaysPolyglutamine tractNeurodegenerative phenotypeAutonomous mannerMechanistic insightsSplicingPotential therapeutic strategyMouse cerebellumExpression
2022
Identifying Disease Signatures in the Spinocerebellar Ataxia Type 1 Mouse Cortex
Luttik K, Olmos V, Owens A, Khan A, Yun J, Driessen T, Lim J. Identifying Disease Signatures in the Spinocerebellar Ataxia Type 1 Mouse Cortex. Cells 2022, 11: 2632. PMID: 36078042, PMCID: PMC9454518, DOI: 10.3390/cells11172632.Peer-Reviewed Original ResearchConceptsSCA1 mouse modelSpinocerebellar ataxia type 1Brain regionsMotor cortexMouse modelPurkinje cellsUnique gene expression changesCranial nerve nucleiBroad brain regionsSpecific neuronal populationsCerebellar Purkinje cellsInferior olive nucleusRegion-specific mechanismsCortical pathologyAtaxin-1Synaptic dysfunctionNerve nucleiSpinocerebellar tractSpinal cordProgressive degenerationTranscriptomic changesNeuronal populationsMouse cortexMutant ataxin-1Type 1Differential effects of Wnt-β-catenin signaling in Purkinje cells and Bergmann glia in spinocerebellar ataxia type 1
Luttik K, Tejwani L, Ju H, Driessen T, Smeets CJLM, Edamakanti CR, Khan A, Yun J, Opal P, Lim J. Differential effects of Wnt-β-catenin signaling in Purkinje cells and Bergmann glia in spinocerebellar ataxia type 1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2208513119. PMID: 35969780, PMCID: PMC9407543, DOI: 10.1073/pnas.2208513119.Peer-Reviewed Original ResearchConceptsWnt-β-cateninSpinocerebellar ataxia type 1Ataxia type 1Cell typesWnt-β-catenin signalingWnt-β-catenin pathwayDifferent cell typesMultiple cell typesSCA1 mouse modelCerebellar cell populationsAtaxin-1Genetic manipulationCerebellar patterningBergmann gliaSCA1 pathogenesisSpecific neuronal populationsPurkinje cellsCerebellar neurodegenerationDistinct responsesCell populationsPathwayNeurodegenerative diseasesMouse cerebellumCritical roleActivationThe extra-cerebellar effects of spinocerebellar ataxia type 1 (SCA1): looking beyond the cerebellum
Olmos V, Gogia N, Luttik K, Haidery F, Lim J. The extra-cerebellar effects of spinocerebellar ataxia type 1 (SCA1): looking beyond the cerebellum. Cellular And Molecular Life Sciences 2022, 79: 404. PMID: 35802260, PMCID: PMC9993484, DOI: 10.1007/s00018-022-04419-7.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSpinocerebellar ataxia type 1Type 1Ataxia type 1Cerebellar Purkinje cell lossProgressive motor deficitsSCA1 patientsPurkinje cell lossMouse model studiesMotor deficitsLimb incoordinationNumber of CAGMouse modelRespiratory problemsMemory impairmentCell lossCerebellar regionsCognitive defectsNeurodegenerative diseasesPatientsAtaxin-1 proteinDiverse pathologiesATXN1 expressionCerebellumDiseaseFurther investigation
2021
Polyglutamine Ataxias: Our Current Molecular Understanding and What the Future Holds for Antisense Therapies
McIntosh C, Li D, Wilton S, Aung-Htut M. Polyglutamine Ataxias: Our Current Molecular Understanding and What the Future Holds for Antisense Therapies. Biomedicines 2021, 9: 1499. PMID: 34829728, PMCID: PMC8615177, DOI: 10.3390/biomedicines9111499.Peer-Reviewed Original ResearchPolyQ spinocerebellar ataxiasAntisense therapyImpaired proteasome functionCAG trinucleotide repeatSpinocerebellar ataxiaHeterogeneous group of neurological disordersGroup of disordersSpinocerebellar ataxia type 1Antisense oligonucleotide therapeuticsPolyQ ataxiasGroup of neurological disordersTrinucleotide repeatsCoding regionClinical presentationProteasome functionPolyglutamine disordersTherapeutic optionsCausative genesClinical trialsDisease progressionHuntington's diseaseProgressive ataxiaTherapeutic approvalsMitochondrial dysfunctionType 1
2020
Pathogenic mechanisms underlying spinocerebellar ataxia type 1
Tejwani L, Lim J. Pathogenic mechanisms underlying spinocerebellar ataxia type 1. Cellular And Molecular Life Sciences 2020, 77: 4015-4029. PMID: 32306062, PMCID: PMC7541529, DOI: 10.1007/s00018-020-03520-z.Peer-Reviewed Original ResearchConceptsGait impairmentSpinocerebellar ataxiaHeterogenous clinical manifestationsProgressive gait impairmentAdditional clinical featuresIon channel dysfunctionKey cellular changesCommon gait impairmentNervous system biologyHereditary cerebellar ataxiaClinical featuresClinical manifestationsCerebellar featuresCerebellar atrophyAutosomal dominant spinocerebellar ataxiaChannel dysfunctionPathogenic mechanismsDisease pathogenesisMolecular pathogenesisCerebellar ataxiaType 1Spinocerebellar ataxia type 1Central mechanismsAtaxia type 1Dominant spinocerebellar ataxias
2018
Molecular pathway analysis towards understanding tissue vulnerability in spinocerebellar ataxia type 1
Driessen TM, Lee PJ, Lim J. Molecular pathway analysis towards understanding tissue vulnerability in spinocerebellar ataxia type 1. ELife 2018, 7: e39981. PMID: 30507379, PMCID: PMC6292693, DOI: 10.7554/elife.39981.Peer-Reviewed Original ResearchConceptsSpinocerebellar ataxia type 1Ataxia type 1Biological pathwaysGene expression changesMolecular pathway analysisSCA1 mouse modelExpression changesPathway analysisMouse modelDisease initiationInferior oliveMolecular alterationsPathwayAffected tissuesSpecific differencesVulnerable tissuesTissue vulnerabilityType 1Different mechanismsGenesTissueOliveFirst time
2013
Polyglutamine Disease Toxicity Is Regulated by Nemo-like Kinase in Spinocerebellar Ataxia Type 1
Ju H, Kokubu H, Todd TW, Kahle JJ, Kim S, Richman R, Chirala K, Orr HT, Zoghbi HY, Lim J. Polyglutamine Disease Toxicity Is Regulated by Nemo-like Kinase in Spinocerebellar Ataxia Type 1. Journal Of Neuroscience 2013, 33: 9328-9336. PMID: 23719801, PMCID: PMC3710458, DOI: 10.1523/jneurosci.3465-12.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedAtaxin-1AtaxinsBehavior, AnimalBlotting, WesternBrainCerebellumChromatography, GelDrosophila melanogasterFemaleGene ExpressionHEK293 CellsHeredodegenerative Disorders, Nervous SystemHumansImmunoprecipitationMiceMice, Inbred C57BLMice, TransgenicMitogen-Activated Protein KinasesNerve Tissue ProteinsNuclear ProteinsPeptidesPhosphorylationProtein Serine-Threonine KinasesSpinocerebellar AtaxiasConceptsNemo-like kinaseSpinocerebellar ataxia type 1Ataxia type 1Enzymatic activitySerine/threonine kinaseDisease toxicityDisease-causing proteinsEffect of NLK
1999
Mutation of the E6-AP Ubiquitin Ligase Reduces Nuclear Inclusion Frequency While Accelerating Polyglutamine-Induced Pathology in SCA1 Mice
Cummings C, Reinstein E, Sun Y, Antalffy B, Jiang Y, Ciechanover A, Orr H, Beaudet A, Zoghbi H. Mutation of the E6-AP Ubiquitin Ligase Reduces Nuclear Inclusion Frequency While Accelerating Polyglutamine-Induced Pathology in SCA1 Mice. Neuron 1999, 24: 879-892. PMID: 10624951, DOI: 10.1016/s0896-6273(00)81035-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxin-1AtaxinsCell NucleusCells, CulturedCysteine EndopeptidasesFluorescent Antibody TechniqueHeLa CellsHumansImmunoblottingImmunohistochemistryInclusion BodiesLigasesMiceMice, KnockoutMicroscopy, ConfocalMultienzyme ComplexesMutationNerve Tissue ProteinsNuclear ProteinsPeptidesPhenotypePlasmidsProteasome Endopeptidase ComplexPurkinje CellsSpinocerebellar DegenerationsUbiquitin-Protein LigasesUbiquitinsConceptsMutant ataxin-1Ataxin-1Spinocerebellar ataxia type 1Ataxin-1 aggregationUbiquitin-protein ligaseUbiquitin-positive nuclear inclusionsUbiquitin-proteasome pathwayNuclear inclusionsPolyglutamine proteinsProteasomal degradationProteasome distributionMutant formsSCA1 pathogenesisAtaxia type 1Patient neuronsPurkinje cell pathologySCA1 miceCell pathologyInclusion frequencyCellsLigasePurkinje cellsProtein
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