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• W2039453997 abstract "Many epidemiological studies suggest that use of non-steroidal anti-inflammatory drugs delays or slows the clinical expression of Alzheimer's disease,[ 13 McGeer P.L Schulzer M McGeer E.G Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology. 1996; 47: 425-432 Crossref PubMed Scopus (1294) Google Scholar ]but the mechanism by which these drugs might affect pathophysiological processes relevant to Alzheimer's disease has been unclear.[ 2 Aisen P.S Davis K.L Inflammatory mechanisms in Alzheimer's disease: implications for therapy. Am. J. Psychiat. 1994; 151: 1105-1113 Crossref PubMed Scopus (314) Google Scholar ]Non-steroidal anti-inflammatory drugs are presumed to act by inhibiting cyclooxygenase, a key enzyme in the metabolism of membrane-derived arachidonic acid into prostaglandins. In recent years, two distinct isoforms of cyclooxygenase have been characterized, a constitutive form, cyclooxygenase-1, and a mitogen-inducible form, cyclooxygenase-2.[ 4 Cao C Matsumura K Yamagata K Watanabe Y Induction by lipopolysaccharide of cyclooxygenase-2 mRNA in rat brain; its possible role in the febrile response. Brain Res. 1995; 697: 187-196 Crossref PubMed Scopus (232) Google Scholar , 10 Kujubu D.A Fletcher B.S Varnum B.C Lim R.W Herschman H.R TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J. biol. Chem. 1991; 266: 12866-12872 Abstract Full Text PDF PubMed Google Scholar , 15 O'Banion M.K Winn V.D Young D.A cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase. Proc. natn. Acad. Sci. U.S.A. 1992; 89: 4888-4892 Crossref PubMed Scopus (804) Google Scholar ]Cyclooxygenase-2 has been identified in rodent brain.[ 1 Adams J Collaço-Moraes Y de Belleroche J Cyclooxygenase-2 induction in cerebral cortex: an intracellular response to synaptic excitation. J. Neurochem. 1996; 66: 6-13 Crossref PubMed Scopus (185) Google Scholar , 8 Kaufmann W.E Worley P.F Pegg J Bremer M Isakson P COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex. Proc. natn. Acad. Sci. U.S.A. 1996; 93: 2317-2321 Crossref PubMed Scopus (565) Google Scholar , 21 Tocco G Freire O Schreiber S.S Sakhi S.H Aisen P.S Pasinetti G.M Maturational regulation and regional induction of cyclooxygenase-2 in rat brain: implications for Alzheimer's disease. Expl Neurol. 1997; 144: 339-349 Crossref PubMed Scopus (168) Google Scholar , 22 Yamagata K Andreasson K.I Kaufmann W.E Barnes C.A Worley P.F Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron. 1993; 11: 371-386 Abstract Full Text PDF PubMed Scopus (1093) Google Scholar ]Excitotoxic lesions cause up-regulation of cyclooxygenase-2 expression coincident with the onset of expression of markers of apoptosis;[ 21 Tocco G Freire O Schreiber S.S Sakhi S.H Aisen P.S Pasinetti G.M Maturational regulation and regional induction of cyclooxygenase-2 in rat brain: implications for Alzheimer's disease. Expl Neurol. 1997; 144: 339-349 Crossref PubMed Scopus (168) Google Scholar ]cyclooxygenase-2 thus represents a possible target of non-steroidal anti-inflammatory drug action in neurodegenerative mechanisms. In the present study, we examined cyclooxygenase-2 gene expression in Alzheimer's disease and control cases. We found up-regulation of cyclooxygenase-2 expression in Alzheimer's disease frontal cortex. Further, we found that synthetic β-amyloid peptides induced cyclooxygenase-2 expression in SH-SY5Y neuroblastoma cells in vitro, suggesting a mechanism for cyclooxygenase-2 up-regulation in Alzheimer's disease. These findings support the investigation of selective cyclooxygenase-2 inhibitors for the treatment of Alzheimer's disease." @default.
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• W2039453997 title "Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer's disease brain" @default.
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• W2039453997 doi "https://doi.org/10.1016/s0306-4522(98)00218-8" @default.
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