title: Altered protein phosphorylation as a resource for potential AD biomarkers.
abstract: The amyloidogenic peptide, Aβ, provokes a series of events affecting distinct cellular pathways regulated by protein phosphorylation. Aβ inhibits protein phosphatases in a dose-dependent manner, thus it is expected that the phosphorylation state of specific proteins would be altered in response to Aβ. In fact several Alzheimer's disease related proteins, such as APP and TAU, exhibit pathology associated hyperphosphorylated states. A systems biology approach was adopted and the phosphoproteome, of primary cortical neuronal cells exposed to Aβ, was evaluated. Phosphorylated proteins were recovered and those whose recovery increased or decreased, upon Aβ exposure across experimental sets, were identified. Significant differences were evident for 141 proteins and investigation of their interactors revealed key protein clusters responsive to Aβ treatment. Of these, 73 phosphorylated proteins increased and 68 decreased upon Aβ addition. These phosphorylated proteins represent an important resource of potential AD phospho biomarkers that should be further pursued.
authors.affiliation: Neuroscience and Signalling Laboratory, Department of Medical Sciences and Insitute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Ana Gabriela
authors.initials: AG
authors.lastname: Henriques
authors.affiliation: Cell Signaling in Neurodegeneration (CSIN), Medical Proteome-Center, Ruhr-University Bochum, 44801 Bochum, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Müller
authors.affiliation: Neuroscience and Signalling Laboratory, Department of Medical Sciences and Insitute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Joana Machado
authors.initials: JM
authors.lastname: Oliveira
authors.affiliation: Neuroscience and Signalling Laboratory, Department of Medical Sciences and Insitute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Cova
authors.affiliation: Laboratório de Instrumentação e Física Experimental de Partículas - LIP, Av. Elias Garcia 14 - 1°, 1000-149 Lisboa, Portugal.
authors.forename: Cristóvão B
authors.initials: CB
authors.lastname: da Cruz E Silva
authors.affiliation: Neuroscience and Signalling Laboratory, Department of Medical Sciences and Insitute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Odete A B
authors.initials: OA
authors.lastname: da Cruz E Silva
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D015415:Biomarkers; D019295:Computational Biology / Q000379:methods; D006801:Humans; D009474:Neurons / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D020543:Proteome; D040901:Proteomics / Q000379:methods; D057188:Workflow
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D010750:Phosphoproteins; D020543:Proteome