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Neurodegener Dis. 2012;10(1-4):46-8. doi: 10.1159/000335914. Epub 2012 Feb 16.

Protein kinase activity profiling of postmortem human brain tissue.

Author information

1
Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.

Abstract

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.

PMID:
22343098
DOI:
10.1159/000335914
[Indexed for MEDLINE]

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