2022
LINE-1 activation in the cerebellum drives ataxia
Takahashi T, Stoiljkovic M, Song E, Gao XB, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu ZW, Kristant A, Zhang Y, Sulkowski P, Glazer PM, Kaczmarek LK, Horvath TL, Iwasaki A. LINE-1 activation in the cerebellum drives ataxia. Neuron 2022, 110: 3278-3287.e8. PMID: 36070749, PMCID: PMC9588660, DOI: 10.1016/j.neuron.2022.08.011.Peer-Reviewed Original ResearchConceptsLINE-1 activationL1 activationAtaxia telangiectasia patientsNuclear element-1Transposable elementsEpigenetic silencersHuman genomeL1 promoterMolecular regulatorsDNA damagePurkinje cell dysfunctionElement 1First direct evidenceTelangiectasia patientsDirect targetingCerebellar expressionNeurodegenerative diseasesDisease etiologyCalcium homeostasis
2016
The need for new approaches in CNS drug discovery: Why drugs have failed, and what can be done to improve outcomes
Gribkoff VK, Kaczmarek LK. The need for new approaches in CNS drug discovery: Why drugs have failed, and what can be done to improve outcomes. Neuropharmacology 2016, 120: 11-19. PMID: 26979921, PMCID: PMC5820030, DOI: 10.1016/j.neuropharm.2016.03.021.Peer-Reviewed Original ResearchConceptsCNS drug discoveryClinical failure rateDisease-modifying treatmentsEffects of drugsMajor neurodegenerative disordersMajor neurodegenerative diseasesNon-CNS drugsFuture CNSCNS diseaseFailure rateCNS disordersCNS targetsBasic research findingsField of neuropharmacologyCNS drugsClinical developmentNeuronal functionNeurological disordersNeurodegenerative disordersNeurodegenerative diseasesHigh failure rateDrug discoveryCNSNew drugsDrugs
2015
Kv3.3 potassium channels and spinocerebellar ataxia
Zhang Y, Kaczmarek LK. Kv3.3 potassium channels and spinocerebellar ataxia. The Journal Of Physiology 2015, 594: 4677-4684. PMID: 26442672, PMCID: PMC4983625, DOI: 10.1113/jp271343.Peer-Reviewed Original ResearchConceptsPurkinje cellsPotassium channelsAuditory brainstem nucleiCentral nervous systemUnique neurodegenerative diseaseCerebellar Purkinje cellsVoltage-dependent potassium channelsSpinocerebellar ataxia type 13Neuronal survivalBrainstem nucleiExtracerebellar symptomsCerebellar degenerationNervous systemNeurodegenerative diseasesComplex spikesNormal functionKv3.3Disease-causing mutationsType 13Kv3.3 potassium channelSpinocerebellar ataxiaHigh rateCerebellumDifferent mutationsPhysiological functions