Cyclooxygenase (COX) catalyses the first committed step in the synthesis of prostanoids, a large family of arachidonic acid metabolites comprising prostaglandins, prostacyclin, and thromboxanes, and is a major target of non-steroidal anti-inflammatory drugs (NSAIDs). COX exists as constitutive and inducible isoforms. COX-2 is the inducible isoform, rapidly expressed in several cell types in response to growth factors, cytokines, and pro-inflammatory molecules. Since its discovery in the early 1990s, COX-2 has emerged as a major player in inflammatory reactions in peripheral tissues. By extension, COX-2 expression in brain has been associated with pro-inflammatory activities, thought to be instrumental in neurodegenerative processes of several acute and chronic diseases. However, 2 major aspects should be borne in mind. First, in the central nervous system, COX-2 is expressed under normal conditions and contributes to fundamental brain functions, such as synaptic activity, memory consolidation, and functional hyperemia. Second, "neuroinflammation" is a much more controlled reaction than inflammation in peripheral tissues, and in many cases is triggered and sustained by activation of resident cells, particularly microglia. In spite of the intense research of the last decade, the evidence of a direct role of COX-2 in neurodegenerative events is still controversial. This article will review new data in this area, focusing on some major human neurological diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson disease, Creutzfeldt-Jakob disease, and Alzheimer disease. Furthermore, the emerging role of COX-2 in behavioral and cognitive functions will be discussed.
NSAIDs block the COX enzymes and reduce production of prostaglandins. Therefore, inflammation, pain, and fever are reduced by all COX inhibitors. Since the prostaglandins that protect the stomach and promote blood clotting also are reduced, NSAIDs can cause ulcers in the stomach and intestines, and increase the risk of bleeding. Unlike older NSAIDs that block both COX-1 and COX-2, the newer COX-2 inhibitors only block the COX-2 enzyme. Since COX-2 inhibitors do not block COX-1 (which primarily produces prostaglandins that protect the stomach and promote blood clotting) they do not cause ulcers or increase the risk of bleeding as much as the older NSAIDs. Nevertheless, COX-2 inhibitors are as effective as the older NSAIDs for treating inflammation, pain and fever.
COX-2 inhibitors have been found to increase the risk of atherothrombosis even with short-term use. A 2006 analysis of 138 randomised trials and almost 150 000 participants  showed that selective COX-2 inhibitors are associated with a moderately increased risk of vascular events, mainly due to a twofold increased risk of myocardial infarction , and also that high-dose regimens of some traditional NSAIDs (such as diclofenac and ibuprofen , but not naproxen ) are associated with a similar increase in risk of vascular events.