LPS-Induced Inflammation Abolishes the Effect of DYRK1A on IkB Stability in the Brain of Mice

Molecular Neurobiology
Alizée LatourNathalie Janel

Abstract

Down syndrome is characterized by premature aging and dementia with neurological features that mimic those found in Alzheimer's disease. This pathology in Down syndrome could be related to inflammation, which plays a role in other neurodegenerative diseases. We previously found a link between the NFkB pathway, long considered a prototypical proinflammatory signaling pathway, and the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). DYRK1A is associated with early onset of Alzheimer's disease in Down syndrome patients. Here, we sought to determine the role of DYRK1A on regulation of the NFkB pathway in the mouse brain. We found that over-expression of Dyrk1A (on a C57BL/6J background) stabilizes IκBα protein levels by inhibition of calpain activity and increases cytoplasmic p65 sequestration in the mouse brain. In contrast, Dyrk1A-deficient mice (on a CD1 background) have decreased IκBα protein levels with an increased calpain activity and decreased cytoplasmic p65 sequestration in the brain. Taken together, our results demonstrate a role of DYRK1A in regulation of the NFkB pathway. However, decreased IκBα and DYRK1A protein levels associated with an increased calpain activity were found in the brains of mi...Continue Reading

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Citations

Feb 26, 2020·International Journal of Molecular Sciences·Yuchen GuNathalie Janel
Jul 10, 2020·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Jean M DelabarMarie-Claude Potier

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Methods Mentioned

BETA
nuclear translocation
FCS
fluorescence activated cell sorting
Protein Assay
immunoprecipitation
PCR
electrophoresis
Protein Translocation
two-hybrid
transgenic

Software Mentioned

Statview
UnScan It

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