2013
Reduction of Synaptojanin 1 Accelerates Aβ Clearance and Attenuates Cognitive Deterioration in an Alzheimer Mouse Model*
Zhu L, Zhong M, Zhao J, Rhee H, Caesar I, Knight E, Volpicelli-Daley L, Bustos V, Netzer W, Liu L, Lucast L, Ehrlich M, Robakis N, Gandy S, Cai D. Reduction of Synaptojanin 1 Accelerates Aβ Clearance and Attenuates Cognitive Deterioration in an Alzheimer Mouse Model*. Journal Of Biological Chemistry 2013, 288: 32050-32063. PMID: 24052255, PMCID: PMC3814799, DOI: 10.1074/jbc.m113.504365.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAnimalsCell Line, TumorDisease Models, AnimalDown-RegulationGene Knockdown TechniquesHippocampusHumansLysosomesMiceMice, TransgenicMutationPeptide FragmentsPhosphatidylinositol 4,5-DiphosphatePhosphoric Monoester HydrolasesPresenilin-1ConceptsAmyloid precursor proteinNovel mechanismSwedish mutant amyloid precursor proteinSynaptojanin 1Aβ clearanceC-terminal fragmentΓ-secretase cleavageMouse modelIntracellular Aβ levelsCellular degradationAlzheimer's Disease Transgenic Mouse ModelFull-length amyloid precursor proteinSYNJ1Cellular clearanceMutant amyloid precursor proteinN2a cellsAlzheimer mouse modelPrecursor proteinTransgenic mouse modelReduced expressionPlaque loadAβ42 levelsAβ levelsTransgenic miceCognitive deterioration
2006
Presenilin-1 uses phospholipase D1 as a negative regulator of β-amyloid formation
Cai D, Netzer WJ, Zhong M, Lin Y, Du G, Frohman M, Foster DA, Sisodia SS, Xu H, Gorelick FS, Greengard P. Presenilin-1 uses phospholipase D1 as a negative regulator of β-amyloid formation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 1941-1946. PMID: 16449386, PMCID: PMC1413665, DOI: 10.1073/pnas.0510708103.Peer-Reviewed Original ResearchMeSH KeywordsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesCell LineEndopeptidasesGene Expression RegulationHumansMembrane ProteinsMiceMice, KnockoutPhospholipase DPresenilin-1Protein BindingProtein Processing, Post-TranslationalProtein TransportTrans-Golgi NetworkConceptsBeta-amyloid precursor proteinPrecursor proteinΒ-amyloid formationAbeta productionAbeta generationPresenilin 1Phospholipase D1 corrects impaired βAPP trafficking and neurite outgrowth in familial Alzheimer’s disease-linked presenilin-1 mutant neurons
Cai D, Zhong M, Wang R, Netzer WJ, Shields D, Zheng H, Sisodia SS, Foster DA, Gorelick FS, Xu H, Greengard P. Phospholipase D1 corrects impaired βAPP trafficking and neurite outgrowth in familial Alzheimer’s disease-linked presenilin-1 mutant neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 1936-1940. PMID: 16449385, PMCID: PMC1413666, DOI: 10.1073/pnas.0510710103.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkOverexpression of PLD1Mutant neuronsPhospholipase D1Beta-amyloid precursor proteinIntracellular traffickingPS1-deficient cellsPLD enzymatic activityTherapeutic targetNeuronal functionPS1 mutationsOverexpression of WTBetaAPPPrecursor proteinMutant cellsSubcellular localizationNeurite outgrowthPLD1 activitySurface deliveryNeuronsOutgrowth capacityCellsTraffickingEnzymatic activityOverexpression