2020
Nemo-like kinase reduces mutant huntingtin levels and mitigates Huntington’s disease
Jiang M, Zhang X, Liu H, LeBron J, Alexandris A, Peng Q, Gu H, Yang F, Li Y, Wang R, Hou Z, Arbez N, Ren Q, Dong JL, Whela E, Wang R, Ratovitski T, Troncoso JC, Mori S, Ross CA, Lim J, Duan W. Nemo-like kinase reduces mutant huntingtin levels and mitigates Huntington’s disease. Human Molecular Genetics 2020, 29: 1340-1352. PMID: 32242231, PMCID: PMC7254850, DOI: 10.1093/hmg/ddaa061.Peer-Reviewed Original ResearchConceptsBrain atrophyHD miceNemo-like kinaseMHTT levelsHD mouse modelsNew molecular targetsHD human brainHuntingtin proteinEffect of NLKMouse striatal cellsFurther mechanistic studiesActivity-dependent mannerHTT protein levelsMouse modelAdult brainStriatal cellsProtective roleMutant Htt aggregationAmino acids 120Huntington's diseaseMutant huntingtin levelsMolecular targetsHuntingtin levelsProtein levelsBrain
1998
In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector
During M, Samulski R, Elsworth J, Kaplitt M, Leone P, Xiao X, Li J, Freese A, Taylor J, Roth R, Sladek J, O’Malley K, Redmond D. In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector. Gene Therapy 1998, 5: 820-827. PMID: 9747462, DOI: 10.1038/sj.gt.3300650.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsAromatic-L-Amino-Acid DecarboxylasesChlorocebus aethiopsDependovirusDopamineDopamine AgentsGene ExpressionGene Transfer TechniquesGenetic VectorsHumansImmunohistochemistryMaleParkinson DiseaseTrigeminal Caudal NucleusTyrosine 3-MonooxygenaseConceptsTyrosine hydroxylaseStriatal cellsDopamine-depleted monkeysAdeno-associated virus vectorProduction of dopamineParkinsonian monkeysTransient feverSevere hyperactivityStriatal dopaminePrimate neuronsStereotactic injectionHistological evidencePrimate modelInjection tractNeurotoxin MPTPDopamine productionParkinson's diseaseTreatment groupsSignificant toxicityBehavioral effectsVivo gene therapyElevated levelsBiochemical effectsFirst dayMonkeys
1985
Low doses of apomorphine elicit two opposing influences on dopamine cell electrophysiology
Grace A, Bunney B. Low doses of apomorphine elicit two opposing influences on dopamine cell electrophysiology. Brain Research 1985, 333: 285-298. PMID: 3995296, DOI: 10.1016/0006-8993(85)91582-3.Peer-Reviewed Original ResearchConceptsDA cell firingDA cellsLow dosesInput resistanceDA agonistsReversal potentialStriatonigral pathwayCell firingCell firing rateElectrophysiological actionsApomorphine effectApomorphine administrationSlow depolarizationIntracellular recordingsIntravenous administrationDopamine cellsInhibitory inputsApomorphineStriatal cellsAction potentialsFiring rateAgonistsDosesCell dischargeCell electrophysiologyOpposing effects of striatonigral feedback pathways on midbrain dopamine cell activity
Grace A, Bunney B. Opposing effects of striatonigral feedback pathways on midbrain dopamine cell activity. Brain Research 1985, 333: 271-284. PMID: 2986775, DOI: 10.1016/0006-8993(85)91581-1.Peer-Reviewed Original ResearchConceptsInhibitory postsynaptic potentialsDA cellsStriatal stimulationReticulata neuronsDA neuronsRebound depolarizationReversal potentialSubstantia nigra zona reticulata neuronsStriatonigral GABAergic pathwayMidbrain dopamine cell activityDopamine cell activitySame stimulation parametersChloride injectionChloride channel blockerChloride reversal potentialSimilar reversal potentialsSimilar time courseGABAergic pathwayGABAergic projectionsZona reticulataPostsynaptic potentialsSystemic injectionChannel blockersIntracellular recordingsStriatal cells
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