2024
Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains
Zhu B, Park J, Coffey S, Russo A, Hsu I, Wang J, Su C, Chang R, Lam T, Gopal P, Ginsberg S, Zhao H, Hafler D, Chandra S, Zhang L. Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains. Science Translational Medicine 2024, 16: eabo1997. PMID: 39475571, DOI: 10.1126/scitranslmed.abo1997.Peer-Reviewed Original ResearchConceptsProteomic analysisAlzheimer's diseasePrefrontal cortexBrain cell typesGenetics of PDParkinson's diseaseCell-cell interactionsChaperone expressionSingle-nucleus transcriptomesExpressed genesTranscriptional changesPostmortem human brainPostmortem brain tissueDiseased brainSynaptic proteinsSingle-cellDown-regulationBrain cell populationsBrain regionsCell typesNeurodegenerative disordersLate-stage PDParkinson's disease brainsDisease etiologyNeuronal vulnerabilityProteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation
Lallai V, Lam T, Garcia-Milian R, Chen Y, Fowler J, Manca L, Piomelli D, Williams K, Nairn A, Fowler C. Proteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation. Biomolecules 2024, 14: 1143. PMID: 39334909, PMCID: PMC11430348, DOI: 10.3390/biom14091143.Peer-Reviewed Original ResearchConceptsImmediate early gene c-fosChronic THC exposureEarly gene c-fosCannabinoid 1 receptorGene c-fosSex-specific mannerTHC exposurePsychoactive componentExtracellular vesiclesCentral signaling mechanismDrug effectsTHCChoroid plexus epithelial cellsFemale ratsC-fosPlexus epithelial cellsBrainCannabisRelease of EVsRegulate intercellular communicationCerebrospinal fluidEpithelial cellsIntercellular signaling mediatorsEV signalingIntercellular communication
2023
The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus
Robert S, Reeves B, Kiziltug E, Duy P, Karimy J, Mansuri M, Marlier A, Allington G, Greenberg A, DeSpenza T, Singh A, Zeng X, Mekbib K, Kundishora A, Nelson-Williams C, Hao L, Zhang J, Lam T, Wilson R, Butler W, Diluna M, Feinberg P, Schafer D, Movahedi K, Tannenbaum A, Koundal S, Chen X, Benveniste H, Limbrick D, Schiff S, Carter B, Gunel M, Simard J, Lifton R, Alper S, Delpire E, Kahle K. The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus. Cell 2023, 186: 764-785.e21. PMID: 36803604, PMCID: PMC10069664, DOI: 10.1016/j.cell.2023.01.017.Peer-Reviewed Original ResearchConceptsPost-infectious hydrocephalusTLR4-dependent immune responseBlood-cerebrospinal fluid barrierSmall molecule pharmacotherapyCell cross talkPharmacological immunomodulationCytokine stormNeuroimmune disordersBrain infectionDrug treatmentImmune responseAcquired hydrocephalusHydrocephalus modelChoroid plexusFluid barrierHydrocephalusEpithelial cellsCSFMulti-omics investigationsCross talkHypersecretionHemorrhagePharmacotherapyImmunomodulationPlexus
2017
Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice
Klein ZA, Takahashi H, Ma M, Stagi M, Zhou M, Lam TT, Strittmatter SM. Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice. Neuron 2017, 95: 281-296.e6. PMID: 28728022, PMCID: PMC5558861, DOI: 10.1016/j.neuron.2017.06.026.Peer-Reviewed Original ResearchConceptsLysosomal protein levelsFrontotemporal lobar degenerationProtein levelsMultiple lysosomal enzymesLysosomal enzymesV0 subunitsTMEM106B geneProteomic analysisProgranulin-deficient miceExtent of neurodegenerationCommon neurodegenerative disorderLysosomal acidificationLysosomal enzyme levelsProtein 1Microglial accumulationRisk modificationFTLD riskBehavioral abnormalitiesRetinal degenerationNeurodegenerative disordersFrontotemporal dementiaGRNTMEM106BFunctional relationshipEnzyme levels
2015
Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation
Henderson MX, Wirak GS, Zhang YQ, Dai F, Ginsberg SD, Dolzhanskaya N, Staropoli JF, Nijssen PC, Lam TT, Roth AF, Davis NG, Dawson G, Velinov M, Chandra SS. Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation. Acta Neuropathologica 2015, 131: 621-637. PMID: 26659577, PMCID: PMC4791186, DOI: 10.1007/s00401-015-1512-2.Peer-Reviewed Original ResearchConceptsNeuronal ceroid lipofuscinosesProtein palmitoylationDisease pathwaysPalmitoyl-protein thioesterase 1Forms of NCLEnzyme palmitoyl-protein thioesterase 1Disease-associated proteinsCommon disease pathwaysNCL genesQuantitative proteomicsCSPα mutationsSpecific enzymatic activityCSPαFunctional linkNeuronal ceroid lipofuscinosisGlobal changePPT1Synaptic proteinsEnzymatic activityCeroid lipofuscinosesPalmitoylationGenesCeroid lipofuscinosisNeurodegenerative disordersProtein
2009
Palmitoylation of Nicotinic Acetylcholine Receptors
Alexander JK, Govind AP, Drisdel RC, Blanton MP, Vallejo Y, Lam TT, Green WN. Palmitoylation of Nicotinic Acetylcholine Receptors. Journal Of Molecular Neuroscience 2009, 40: 12-20. PMID: 19693711, PMCID: PMC3523180, DOI: 10.1007/s12031-009-9246-z.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAcylationAlpha7 Nicotinic Acetylcholine ReceptorAnimalsBinding SitesBiological AssayBrainCell LineElectric OrganHumansLigandsLipoylationMass SpectrometryNeuromuscular JunctionProtein Processing, Post-TranslationalProtein SubunitsProtein TransportReceptors, NicotinicSynaptic TransmissionTorpedoConceptsNicotinic acetylcholine receptorsSites of palmitoylationLigand-gated ion channelsDifferent posttranslational modificationsDisulfide bond formationMass spectrometry strategyLigand binding siteLow abundant proteinsAcetylcholine receptorsProtein palmitoylationPosttranslational modificationsSubunit assemblyPalmitoylationAbundant proteinsMuscle-type nAChRsIon channelsLoss of ligandBinding sitesSubunitsSitesReceptorsPhosphorylationTraffickingGlycosylationSensitive assay