2017
Bidirectional regulation of Aβ levels by Presenilin 1
Bustos V, Pulina MV, Kelahmetoglu Y, Sinha SC, Gorelick FS, Flajolet M, Greengard P. Bidirectional regulation of Aβ levels by Presenilin 1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 7142-7147. PMID: 28533411, PMCID: PMC5502639, DOI: 10.1073/pnas.1705235114.Peer-Reviewed Original ResearchConceptsAmyloid precursor proteinAβ levelsΓ-secretase complexAlzheimer's diseasePresenilin 1Pathogenesis of ADAβ peptidesEndogenous kinaseΒ-amyloid peptidePS1 functionIntramembranous proteinsCatalytic subunitΓ-secretase activityPlaque loadC-terminal fragmentAutophagic degradationPotential therapySer367Selective phosphorylationSequential proteolysisTransgenic micePhosphorylationCultured cellsΒ-secretaseDiseasePhosphorylated Presenilin 1 decreases β-amyloid by facilitating autophagosome–lysosome fusion
Bustos V, Pulina MV, Bispo A, Lam A, Flajolet M, Gorelick FS, Greengard P. Phosphorylated Presenilin 1 decreases β-amyloid by facilitating autophagosome–lysosome fusion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 7148-7153. PMID: 28533369, PMCID: PMC5502640, DOI: 10.1073/pnas.1705240114.Peer-Reviewed Original Research
2010
Gamma-secretase activating protein is a therapeutic target for Alzheimer’s disease
He G, Luo W, Li P, Remmers C, Netzer WJ, Hendrick J, Bettayeb K, Flajolet M, Gorelick F, Wennogle LP, Greengard P. Gamma-secretase activating protein is a therapeutic target for Alzheimer’s disease. Nature 2010, 467: 95-98. PMID: 20811458, PMCID: PMC2936959, DOI: 10.1038/nature09325.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseGamma-secretase activating proteinDisease drugsBlood-brain barrierSevere side effectsΓ-secretase activating proteinPossible new targetsAlzheimer's disease drugsNotch cleavageSide effectsTherapeutic targetActivating proteinHomeostatic functionsAnti-Alzheimer drugsDiseaseNew targetsΓ-secretaseAnticancer drug imatinibProcessing of NotchDrugsDrug imatinibImatinibBrain
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 Network