Is cyclooxygenase‐1 involved in neuroinflammation?

Abstract

Purpose: Reactive microglia are an important hallmark of neuroinflammation. Reactive microglia release various inflammatory mediators, such as cytokines, chemokines, and prostaglandins, which are produced by enzymes like cyclooxygenases (COX). The inducible COX‐2 subtype has been associated with inflammation, whereas the constitutively expressed COX‐1 subtype is generally considered as a housekeeping enzyme. However, recent evidence suggests that COX‐1 can also be upregulated and may play a prominent role in the brain during neuroinflammation. In this review, we summarize the evidence that supports this involvement of COX‐1. Methods: Five databases were used to retrieve relevant studies that addressed COX‐1 in the context of neuroinflammation. The search resulted in 32 articles, describing in vitro, in vivo, post mortem, and in vivo imaging studies that specifically investigated the COX‐1 isoform under such conditions. Results: Reviewed literature generally indicated that the overexpression of COX‐1 was induced by an inflammatory stimulus, which resulted in an increased production of prostaglandin E2. The pharmacological inhibition of COX‐1 was shown to suppress the induction of inflammatory mediators like prostaglandin E2. Positron emission tomography (PET) imaging studies in animal models confirmed the overexpression of COX‐1 during neuroinflammation. The same imaging method, however, could not detect any upregulation of COX‐1 in patients with Alzheimer's disease. Conclusion: Taken together, studies in cultured cells and living rodents suggest that COX‐1 is involved in neuroinflammation. Most postmortem studies on human brains indicate that the concentration of COX‐1‐expressing microglial cells is increased near sites of inflammation. However, evidence for the involvement of COX‐1 in neuroinflammation in the living human brain is still largely lacking.

A Randomized Double-Blind Comparative Study of Efficacy and Safety Between Low-Dose Etoricoxib and Ibuprofen Coadministered with Low-Dose Paracetamol for Dental Pain

“…19 Furthermore, COX-1 generated prostaglandins also play some role in producing inflammation, and the addition of paracetamol with etoricoxib broadens the efficacy of COX-2 inhibitor etoricoxib more than that of therapeutic dose ibuprofen. 20 In the present study on comparison of safety, it was observed that none of the patients reported any severe adverse reactions in both groups. Mild to moderate adverse drug reactions were reported in 10% of the etoricoxib-treated group and 20% of the ibuprofen-treated group, suggesting that etoricoxib is an overall safer drug than ibuprofen.…”

“…19 Furthermore, COX-1 generated prostaglandins also play some role in producing inflammation, and the addition of paracetamol with etoricoxib broadens the efficacy of COX-2 inhibitor etoricoxib more than that of therapeutic dose ibuprofen. 20…”

Allicin, an Antioxidant and Neuroprotective Agent, Ameliorates Cognitive Impairment

“…A neuroinflammatory mediator PGE2is produced from PGH2 [ 123 , 124 ]. COX II has more prominent role in the induction of neuroinflammation and COX I is generally considered as the house keeping enzyme [ 125 ].…”

Preliminary Assessment of the Anti-inflammatory Activity of New Structural Honokiol Analogs with a 4′-O-(2-Fluoroethyl) Moiety and the Potential of Their 18F-Labeled Derivatives for Neuroinflammation Imaging

“…Scheme 1B summarizes the chemistry used to prepare new honokiol structural analogs (F-I-F-IV)-potential anti-inflammation agents. The key step in the synthesis of these biphenyls was a Suzuki-Miyaura cross-coupling reaction of aryl iodides (3) or bromides (4,11) with aryl boronic compounds. The resulting intermediates (5, 8, 12, 15) were converted into fluoroethoxy compounds (6, 9, 13, 16), which were then deprotected with HCl acid.…”

“…Both known isoforms, COX-1 and COX-2, are expressed in the brain. COX-1 is constitutively expressed in the CNS (as a "house-keeping" enzyme) and is not upregulated by inflammation, although some studies have shown that COX-1 may play a prominent role in neuroinflammation [4]. The inducible type of cyclooxygenase COX-2 is rapidly and dramatically overexpressed under inflammatory conditions and, therefore, is one of the most attractive molecular targets for PET imaging of neuroinflammation.…”