Thinking outside the box about COX-1 in Alzheimer's disease.
This article from Coma et al. shows that a salicylic acid derivative Triflusal, a platelet aggregation inhibitor and irreversible inhibitor of COX-1, can correct defects in axonal curvature and cognition in an AD transgenic mouse model (Tg2576) (Coma et al., 2010). Here we discuss the controversy over the role of COX-1 in AD, which has not been considered carefully in part due to the presumed adverse gastrointestinal effects of COX-1 antagonism. However, recent clinical data from this group as well as other groups challenges this assumption that COX-1 antagonism will be associated with side effects. Most importantly this article raises critical questions about the role of COX-1, versus COX-2 versus both in Abeta pathogenesis. The animal model data in this article as well as the recently published trial data suggest that COX-1 may play an important role in early pathogenesis and should not be ignored as a potential target for early intervention.
Frautschy
Sally A
SA
Greater Los Angeles Healthcare System, Geriatric Research Education and Clinical Center, Veteran's Affairs Medical Center, North Hills, CA 91343, USA. frautsch@ucla.edu
D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002491:Central Nervous System Agents / Q000009:adverse effects / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D012459:Salicylates / Q000009:adverse effects / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D002491:Central Nervous System Agents; D052246:Cyclooxygenase 2 Inhibitors; D008565:Membrane Proteins; D012459:Salicylates; C016167:triflusal; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; C496512:Ptgs1 protein, mouse