2023
Reduction 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
Differential 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 roleActivation
2021
Microglia regulate brain Progranulin levels through the endocytosis-lysosomal pathway
Dong T, Tejwani L, Jung Y, Kokubu H, Luttik K, Driessen TM, Lim J. Microglia regulate brain Progranulin levels through the endocytosis-lysosomal pathway. JCI Insight 2021, 6: e136147. PMID: 34618685, PMCID: PMC8663778, DOI: 10.1172/jci.insight.136147.Peer-Reviewed Original ResearchConceptsPGRN levelsNovel potential therapeutic targetFrontotemporal lobar degenerationPotential therapeutic targetNeuronal ceroid lipofuscinosisPGRN deficiencyPGRN expressionLysosomal pathwayProgranulin levelsPathological changesHaploinsufficient miceTherapeutic targetMicrogliaNeuropathological phenotypeAlzheimer's diseaseProgranulinCeroid lipofuscinosisGlycoprotein progranulinNeurodegenerative diseasesDiseaseMiceGenetic alterationsNemo-like kinaseGenetic interaction studiesGenetic variants
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
2017
Hunting for the mutant without the MAP(K)
Tejwani L, Lim J. Hunting for the mutant without the MAP(K). Cell Research 2017, 27: 1403-1404. PMID: 29134957, PMCID: PMC5717406, DOI: 10.1038/cr.2017.140.Peer-Reviewed Original Research