Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice
- PMID: 27425247
- DOI: 10.1016/j.bbrc.2016.07.015
Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice
Abstract
Epidemiologic studies indicate that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk for developing Alzheimer's disease (AD). Because the primary mode of action of NSAIDs is to inhibit cyclooxygenase (COX) activity, it has been proposed that perturbed activity of COX-1 or COX-2 contributes to AD pathogenesis. To test the role of COX-1 or COX-2 in amyloid deposition and amyloid-associated inflammatory changes, we examined amyloid precursor protein (APP) transgenic mice in the context of either COX-1 or COX-2 deficiency. Our studies showed that loss of either COX-1 or COX-2 gene did not alter amyloid burden in brains of the APP transgenic mice. However, one marker of microglial activation (CD45) was decreased in brains of COX-1 deficient/APP animals and showed a strong trend in reduction in COX-2 deficient/APP animals. These results suggest that COX activity and amyloid deposition in brain are likely independent processes. Further, if NSAIDs do causally reduce the risks of AD, then our findings indicate that the mechanisms are likely not due primarily to their inhibition on COX or γ-secretase modulation activity, the latter reported recently after acute dosing of ibuprofen in humans and nonhuman primates.
Keywords: Alzheimer's disease; Amyloid β protein; Cyclooxygenase; Microglia; Transgenic mice.
Copyright © 2016. Published by Elsevier Inc.
Similar articles
-
In vitro and in vivo profiling of CHF5022 and CHF5074 Two beta-amyloid1-42 lowering agents.Pharmacol Res. 2007 Apr;55(4):318-28. doi: 10.1016/j.phrs.2006.12.010. Epub 2007 Jan 16. Pharmacol Res. 2007. PMID: 17292621
-
Relationship between ubiquilin-1 and BACE1 in human Alzheimer's disease and APdE9 transgenic mouse brain and cell-based models.Neurobiol Dis. 2016 Jan;85:187-205. doi: 10.1016/j.nbd.2015.11.005. Epub 2015 Nov 10. Neurobiol Dis. 2016. PMID: 26563932
-
Anti-inflammatory drug therapy alters beta-amyloid processing and deposition in an animal model of Alzheimer's disease.J Neurosci. 2003 Aug 20;23(20):7504-9. doi: 10.1523/JNEUROSCI.23-20-07504.2003. J Neurosci. 2003. PMID: 12930788 Free PMC article.
-
Cyclooxygenase-1 and -2 in the different stages of Alzheimer's disease pathology.Curr Pharm Des. 2008;14(14):1419-27. doi: 10.2174/138161208784480171. Curr Pharm Des. 2008. PMID: 18537664 Review.
-
Regulation of APP synthesis and secretion by neuroimmunophilin ligands and cyclooxygenase inhibitors.Ann N Y Acad Sci. 2000;920:261-8. doi: 10.1111/j.1749-6632.2000.tb06934.x. Ann N Y Acad Sci. 2000. PMID: 11193162 Review.
Cited by
-
Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer's Disease.Int J Mol Sci. 2019 Oct 14;20(20):5090. doi: 10.3390/ijms20205090. Int J Mol Sci. 2019. PMID: 31615073 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous