BACKGROUND: Identification of signal transduction pathways that are critically involved in Alzheimer's disease (AD) is essential for the development of disease-specific biomarkers and drug therapy. OBJECTIVE: This study is aimed at identifying protein kinases and signaling pathways that are activated in AD pathology. METHODS: Microarray-based kinome profiling was employed for the detection of protein kinase activity in postmortem brain tissue derived from AD and age-matched nondemented control cases. Global serine/threonine kinase activity profiles are identified applying a peptide array system consisting of 140 peptides derived from known kinase substrate sequences covalently attached to porous chips, through which a protein solution is constantly pumped up and down. Peptide phosphorylation is determined by measuring the association of a mixture of fluorescently labeled antibodies, raised against phosphoserine- or phosphothreonine-containing peptides. RESULTS: Protein lysates from freshly frozen postmortem brain tissue from nondemented controls and pathologically confirmed AD cases show ATP-dependent phosphorylation of peptides. In AD and control cases, peptides that are differentially phosphorylated are identified. CONCLUSION: Protein kinase activity profiling can be used to reveal novel kinases and new signaling pathways involved in AD pathology.
BACKGROUND: Identification of signal transduction pathways that are critically involved in Alzheimer's disease (AD) is essential for the development of disease-specific biomarkers and drug therapy. OBJECTIVE: This study is aimed at identifying protein kinases and signaling pathways that are activated in AD pathology. METHODS: Microarray-based kinome profiling was employed for the detection of protein kinase activity in postmortem brain tissue derived from AD and age-matched nondemented control cases. Global serine/threonine kinase activity profiles are identified applying a peptide array system consisting of 140 peptides derived from known kinase substrate sequences covalently attached to porous chips, through which a protein solution is constantly pumped up and down. Peptide phosphorylation is determined by measuring the association of a mixture of fluorescently labeled antibodies, raised against phosphoserine- or phosphothreonine-containing peptides. RESULTS: Protein lysates from freshly frozen postmortem brain tissue from nondemented controls and pathologically confirmed AD cases show ATP-dependent phosphorylation of peptides. In AD and control cases, peptides that are differentially phosphorylated are identified. CONCLUSION: Protein kinase activity profiling can be used to reveal novel kinases and new signaling pathways involved in AD pathology.
Authors: Pekka Määttänen; Brett Trost; Erin Scruten; Andrew Potter; Anthony Kusalik; Philip Griebel; Scott Napper Journal: Infect Immun Date: 2013-05-28 Impact factor: 3.441
Authors: Andrea F N Rosenberger; Riet Hilhorst; Elisabeth Coart; Leandro García Barrado; Faris Naji; Annemieke J M Rozemuller; Wiesje M van der Flier; Philip Scheltens; Jeroen J M Hoozemans; Saskia M van der Vies Journal: J Alzheimers Dis Date: 2016 Impact factor: 4.472
Authors: Alex M Dussaq; Timothy Kennell; Nicholas J Eustace; Joshua C Anderson; Jonas S Almeida; Christopher D Willey Journal: PLoS One Date: 2018-08-21 Impact factor: 3.240