Choi Sang-Ho, Aid Saba, Bosetti Francesca
Molecular Neuroscience Unit, Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Trends Pharmacol Sci. 2009 Apr;30(4):174-81. doi: 10.1016/j.tips.2009.01.002. Epub 2009 Mar 9.
Cyclooxygenases (COX-1 and COX-2) are key enzymes in the conversion of arachidonic acid to prostaglandins and other lipid mediators. Because it can be induced by inflammatory stimuli, COX-2 has been classically considered as the most appropriate target for anti-inflammatory drugs. However, recent data indicate that COX-2 can mediate neuroprotection and that COX-1 is a major player in the neuroinflammatory process. We discuss the specific contributions of COX-1 and COX-2 in various neurodegenerative diseases and in models of neuroinflammation. We suggest that, owing to its predominant localization in microglia, COX-1 might be the major player in neuroinflammation, whereas COX-2, which is localized in neurons, might have a major role in models in which the neurons are directly challenged. Overall, the benefit of using COX-2 inhibitors should be carefully evaluated and COX-1 preferential inhibitors should be further investigated as a potential therapeutic approach in neurodegenerative diseases with an inflammatory component.
环氧化酶（COX - 1和COX - 2）是将花生四烯酸转化为前列腺素和其他脂质介质的关键酶。由于COX - 2可被炎症刺激诱导，传统上它被认为是抗炎药物的最合适靶点。然而，最近的数据表明COX - 2可介导神经保护作用，而COX - 1是神经炎症过程中的主要参与者。我们讨论了COX - 1和COX - 2在各种神经退行性疾病和神经炎症模型中的具体作用。我们认为，由于COX - 1主要定位于小胶质细胞，它可能是神经炎症的主要参与者，而位于神经元中的COX - 2可能在神经元直接受到挑战的模型中起主要作用。总体而言，使用COX - 2抑制剂的益处应仔细评估，COX - 1优先抑制剂作为具有炎症成分的神经退行性疾病的潜在治疗方法应进一步研究。
