Neurones treated with cyclo-oxygenase-1 inhibitors are resistant to amyloid-beta1-42.
Epidemiological studies have shown that the risk of developing Alzheimer's disease is reduced by the chronic use of classical non-steroidal anti-inflammatory drugs (NSAIDs), drugs that inhibit the cyclo-oxygenase (COX) enzymes that convert arachidonic acid to prostaglandins. In the present study, human SH-SY5Y neuroblastoma cells or murine primary cortical neurones treated with NSAIDs were protected against the otherwise toxic effects of amyloid-beta1-42. COX-1 selective inhibitors provided greater protection than did COX-2 selective inhibitors or lipoxygenase inhibitors, suggesting that activation of COX-1 is required for amyloid-beta1-42-induced neurotoxicity. Although the production of neuronal prostaglandin E2 in response to amyloid-beta1-42 was reduced by the presence of COX-1 inhibitors, no neurotoxic effects of prostaglandin E2, or any other prostaglandin, were observed.
Institute of Comparative Medicine, Department of Veterinary Pathology, Glasgow University Veterinary School, Bearsden Road, Glasgow G61 1QH, UK. c.bate@vet.gla.ac.uk
Clive
C
Bate
Robert
R
Veerhuis
Piet
P
Eikelenboom
Alun
A
Williams
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D004351:Drug Resistance / Q000187:drug effects / Q000502:physiology; D005333:Fetus; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D008084:Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone