Aspirin and non-steroidal anti-inflammatory drugs inhibit amyloid-beta aggregation.
The neurotoxic and proinflammatory actions of the Alzheimer peptide amyloid-beta (Abeta) are dependent on its aggregation and beta-sheet conformation. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin for arthritis decreases the risk of developing Alzheimer's disease (AD) by unknown mechanisms. We report that these drugs inhibit human Abeta aggregation in vitro and reverse the beta-sheet conformation of preformed fibrils at clinically relevant doses. Aspirin prevented enhanced Abeta aggregation by aluminum, an environmental risk factor for AD. This anti-aggregatory effect was restricted to NSAIDs and was not exhibited by other drugs used in AD therapy. NSAIDS may have a role in the prevention and treatment of AD, in addition to a number of age-related disorders such as arthritis, cardiovascular disease and cancer.
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Woodlands Medical Center and Endron Therapeutics, 3150 Tampa Road, #16 Oldsmar, FL 34677, USA.
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D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D000068579:Celecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008565:Membrane Proteins; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D058225:Plaque, Amyloid / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D010446:Peptide Fragments; D011720:Pyrazoles; D013449:Sulfonamides; C074636:amyloid beta-protein (25-35); D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D001241:Aspirin