Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer's disease brain.
Many epidemiological studies suggest that use of nonsteroidal anti-inflammatory drugs delays or slows the clinical expression of Alzheimer's disease, but the mechanism by which these drugs might affect pathophysiological processes relevant to Alzheimer's disease has been unclear. 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. Cyclooxygenase-2 has been identified in rodent brain. Excitotoxic lesions cause up-regulation of cyclooxygenase-2 expression coincident with the onset of expression of markers of apoptosis; 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 beta-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.
Pasinetti
G M
GM
Department of Psychiatry, Brookdale Center for Molecular Biology, The Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Aisen
P S
PS
D000544:Alzheimer Disease / Q000201:enzymology*; D015152:Blotting, Northern; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D009474:Neurons / Q000201:enzymology; D017397:Prefrontal Cortex / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases