It has been reported that inhibition of COX-2 beside traditional effects of NSAIDs, reduces the risk of colorectal, breast and lung cancers and also slow the progress of Alzheimer's disease.Zarghi et al. reported 8-benzoyl-2-(4-(methylsulfonyl)phenyl)quinoline-4-carboxylic acid (AZGH 102) as a novel compound with similar IC50 to celecoxib besides improved selectivity index (COX-1/COX-2 inhibitory potency) in comparison with celecoxib.
We thus synthesized (11)C-labeled (S)-ketoprofen methyl ester ((S)-(11)C-KTP-Me) as an improved PET probe specific for COX-1 and applied it for investigation of the changes in COX-1 during the progression of AD in a mouse model.
As NSAIDs inhibit the enzymatic activity of the inflammatory cyclooxygenases COX-1 and COX-2, these findings suggest that downstream prostaglandin signaling pathways function in the preclinical development of AD.
Because the inhibition of COX-1 is also known to cause tissue damage in the gastrointestinal system from the resultant reduced cytoprotection, selective COX-2 inhibitors are being investigated and tested clinically as potentially better therapeutics for AD patients.
Our results indicate that in short PMI brain, COX-1 and COX-2 transcripts are relatively low abundance RNA messages, ranging from a mean of 6.8% of the beta-actin signal in controls to 8.5% of the beta-actin signal in AD-affected brain.