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Increased occurrence of protein kinase CK2 in astrocytes in Alzheimer’s disease pathology

Authors :
Andrea F.N. Rosenberger
Philip Scheltens
Riet Hilhorst
Annemieke J.M. Rozemuller
Jeroen J.M. Hoozemans
Elise S. van Haastert
Wouter H. Gerritsen
Hripsime Snkhchyan
Tjado H. J. Morrema
Saskia M. van der Vies
Neurology
Pathology
Amsterdam Neuroscience - Neurodegeneration
Source :
Journal of Neuroinflammation, 13:4. BioMed Central, Journal of Neuroinflammation, Rosenberger, A F N, Morrema, T H J, Gerritsen, W H, van Haastert, E S, Snkhchyan, H, Hilhorst, R, Rozemuller, A J M, Scheltens, P, van der Vies, S M & Hoozemans, J J M 2016, ' Increased occurrence of protein kinase CK2 in astrocytes in Alzheimer's disease pathology ', Journal of Neuroinflammation, vol. 13, 4 . https://doi.org/10.1186/s12974-015-0470-x
Publisher :
Springer Nature

Abstract

Background Alzheimer’s disease (AD) is the most common neurodegenerative disease. In addition to the occurrence of amyloid deposits and widespread tau pathology, AD is associated with a neuroinflammatory response characterized by the activation of microglia and astrocytes. Protein kinase 2 (CK2, former casein kinase II) is involved in a wide variety of cellular processes. Previous studies on CK2 in AD showed controversial results, and the involvement of CK2 in neuroinflammation in AD remains elusive. Methods In this study, we used immunohistochemical and immunofluorescent staining methods to investigate the localization of CK2 in the hippocampus and temporal cortex of patients with AD and non-demented controls. We compared protein levels with Western blotting analysis, and we investigated CK2 activity in human U373 astrocytoma cells and human primary adult astrocytes stimulated with IL-1β or TNF-α. Results We report increased levels of CK2 in the hippocampus and temporal cortex of AD patients compared to non-demented controls. Immunohistochemical analysis shows CK2 immunoreactivity in astrocytes in AD and control cases. In AD, the presence of CK2 immunoreactive astrocytes is increased. CK2 immunopositive astrocytes are associated with amyloid deposits, suggesting an involvement of CK2 in the neuroinflammatory response. In U373 cells and human primary astrocytes, the selective CK2 inhibitor CX-4945 shows a dose-dependent reduction of the IL-1β or TNF-α induced MCP-1 and IL-6 secretion. Conclusions This data suggests that CK2 in astrocytes is involved in the neuroinflammatory response in AD. The reduction in pro-inflammatory cytokine secretion by human astrocytes using the selective CK2 inhibitor CX-4945 indicates that CK2 could be a potential target to modulate neuroinflammation in AD. Electronic supplementary material The online version of this article (doi:10.1186/s12974-015-0470-x) contains supplementary material, which is available to authorized users.

Details

Language :
English
ISSN :
17422094
Volume :
13
Issue :
1
Database :
OpenAIRE
Journal :
Journal of Neuroinflammation
Accession number :
edsair.doi.dedup.....1c63417ea05057dab4939592e54a1a20
Full Text :
https://doi.org/10.1186/s12974-015-0470-x