Abstract
BackgroundAlzheimer’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.MethodsIn 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.ResultsWe 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.ConclusionsThis 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 materialThe online version of this article (doi:10.1186/s12974-015-0470-x) contains supplementary material, which is available to authorized users.
Highlights
Alzheimer’s disease (AD) is the most common neurodegenerative disease
Rosenberger et al Journal of Neuroinflammation (2016) 13:4 In AD, neuroinflammation is associated with an increase of activated complement proteins and cytokines, such as interleukin 6 (IL-6) and monocyte chemotactic protein-1 (MCP-1; referred to as chemokine (C-C motif ) ligand 2 (CCL2)), and activated microglia and astrocytes [4, 5]
CK2 protein levels are increased in AD brain CK2 protein levels were assessed by Western blot analysis using brain tissue extracts of the temporal cortex and hippocampus of AD and non-demented control cases (CON; Table 1)
Summary
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. In AD, neuroinflammation is associated with an increase of activated complement proteins and cytokines, such as interleukin 6 (IL-6) and monocyte chemotactic protein-1 (MCP-1; referred to as chemokine (C-C motif ) ligand 2 (CCL2)), and activated microglia and astrocytes [4, 5] These markers are already present in the cerebral cortex at early stages of AD pathology [6,7,8]. Among the genes that increase the risk of developing AD, several are associated with inflammation, for instance TREM2, CD33, CR1 and CLU [9,10,11,12,13,14] As such inflammation is considered an integral part of AD pathology [9, 10] and is characterized as a local activation of the innate immune response, referred to as neuroinflammation. It is thought that the neuroinflammatory response in AD is aimed at eliminating injurious stimuli and restoring tissue integrity
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