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- Title
Selective inhibition of Aβ42 production by NSAID R -enantiomers.
- Authors
Morihara, T.; Chu, T.; Ubeda, O.; Beech, W.; Cole, G. M.
- Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk for Alzheimer's disease (AD) and selected NSAIDs racemates suppress β-amyloid (Aβ) accumulation in vivo and Aβ42 production in vitro. Clinical use of NSAIDs for preventing or treating AD has been hampered by dose-limiting toxicity believed to be due to cyclooxygenase (COX)-inhibition that is reportedly not essential for selective Aβ42 reduction. Profens have racemates and R-enantiomers were supposed to be inactive forms. Here we demonstrate that R-ibuprofen and R-flurbiprofen, with poor COX-inhibiting activity, reduce Aβ42 production by human cells. Although these R-enantiomers inhibit nuclear factorκB (NF-κB) activation and NF-κB can selectively regulate Aβ42, Aβ42 reduction is not mediated by inhibition of NF-κB activation. Because of its efficacy at lowering Aβ42 production and low toxicity profile, R-flurbiprofen is a strong candidate for clinical development.
- Subjects
AMYLOID beta-protein; NONSTEROIDAL anti-inflammatory agents; NF-kappa B; ALZHEIMER'S disease
- Publication
Journal of Neurochemistry, 2002, Vol 83, Issue 4, p1009
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2002.01195.x