Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice.
Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice.
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DOI：
10.1016/j.bbrc.2016.07.015
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发表时间：
2016-09
影响因子：
3.1
通讯作者：
S. A. Park;N. Chevallier;Karishma Tejwani;Mary M Hung;H. Maruyama;T. Golde;E. Koo
中科院分区：
文献类型：
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作者：
S. A. Park;N. Chevallier;Karishma Tejwani;Mary M Hung;H. Maruyama;T. Golde;E. Koo
流行病学研究表明，长期使用非甾体抗炎药 (NSAID) 与降低患阿尔茨海默病 (AD) 的风险相关。由于 NSAID 的主要作用方式是抑制环氧合酶 (COX) 活性，因此有人提出，COX-1 或 COX-2 的活性紊乱会导致 AD 发病机制。为了测试 COX-1 或 COX-2 在淀粉样蛋白沉积和淀粉样蛋白相关炎症变化中的作用，我们在 COX-1 或 COX-2 缺乏的情况下检查了淀粉样蛋白前体蛋白 (APP) 转基因小鼠。我们的研究表明，COX-1 或 COX-2 基因的缺失不会改变 APP 转基因小鼠大脑中淀粉样蛋白的负荷。然而，COX-1 缺陷/APP 动物的大脑中小胶质细胞激活的一种标志物 (CD45) 减少，并且在 COX-2 缺陷/APP 动物的大脑中显示出强烈的减少趋势。这些结果表明 COX 活性和大脑中淀粉样蛋白沉积可能是独立的过程。此外，如果 NSAID 确实降低了 AD 风险，那么我们的研究结果表明，该机制可能主要不是由于它们对 COX 或 γ-分泌酶调节活性的抑制，后者是最近在人类和非人类灵长类动物中急性服用布洛芬后报道的。
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 eitherCOX-1orCOX-2gene 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.