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

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 IB 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 IB 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 IB and DYRK1A protein levels associated with an increased calpain activity were found in the brains of mice over-expressing Dyrk1A after lipopolysaccharide treatment. Although inflammation induced by lipopolysaccharide treatment has a positive effect on calpastatin and a negative effect on DYRK1A protein level, a positive effect on microglial activation is maintained in the brains of mice over-expressing Dyrk1A.
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https://hal-cnrs.archives-ouvertes.fr/hal-03201563
Contributor : Colette Orange <>
Submitted on : Monday, April 19, 2021 - 8:58:23 AM
Last modification on : Wednesday, April 21, 2021 - 3:23:35 AM

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Alizee Latour, Yuchen Gu, Nadim Kassis, Fabrice Daubigney, Catherine Colin, et al.. LPS-Induced Inflammation Abolishes the Effect of DYRK1A on IkB Stability in the Brain of Mice. Molecular Neurobiology, Humana Press, 2019, 56 (2), pp.963-975. ⟨10.1007/s12035-018-1113-x⟩. ⟨hal-03201563⟩

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