CYCLOOXYGENASES (COXS) are key enzymes in the conversion of arachidonic acid to prostanoids, which mediate mitogenesis, apoptosis, angiogenesis, blood flow, secondary injury (lipid peroxidation and oxidative stress), and inflammation.1,2 Although COX-1 and COX-2 are remarkably identical in enzymatic function and protein structure, a clear functional demarcation has been proposed.2 The COX-1 isoform is expressed constitutively under physiological conditions, but the inducible COX-2 isoform is strongly expressed under pathophysiological, mainly inflammatory, conditions.2 Consequently, the current pharmacological strategy is to selectively inhibit COX-2 and thereby avoid some common adverse effects of combined COX-1 and COX-2 blocking, such as ulcer bleeding. However, these concepts have been challenged recently, and it has been revealed, paradoxically, that acetylated COX-2 also exerts anti-inflammatory effects during resolution of inflammation3,4 or performs physiological functions during wound healing in ulcers.5 Therefore, a more pronounced role in inflammatory responses is being envisioned for the conceptually neglected COX-1 isoform, and a specific role in pain conduction has been attributed to the related protein COX-3, which is encoded by the COX-1 gene.6 Long-term accumulation of COX-1–expressing monocytic microglia and macrophages is evident in brain ischemic and traumatic lesions,7-9 and similar observations were reported in β-amyloid plaques and in Alzheimer disease fusiform cortex, indicating areas of Alzheimer disease neurodegeneration.10
Schwab JM, Schluesener HJ. Cyclooxygenases and Central Nervous System Inflammation: Conceptual Neglect of Cyclooxygenase 1. Arch Neurol. 2003;60(4):630–632. doi:10.1001/archneur.60.4.630
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