Journal
JOURNAL OF NEUROCHEMISTRY
Volume 83, Issue 4, Pages 1009-1012Publisher
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.1471-4159.2002.01195.x
Keywords
Alzheimer's disease; beta-amyloid; non-steroidal anti-inflammatory drugs (NSAIDs); nuclear factor-kappa B (NF-kappa B); R-flurbiprofen; R-ibuprofen
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Funding
- NIA NIH HHS [AG13471] Funding Source: Medline
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Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk for Alzheimer's disease (AD) and selected NSAIDs racemates suppress beta-amyloid (Abeta) accumulation in vivo and Abeta42 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 Abeta42 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 Abeta42 production by human cells. Although these R-enantiomers inhibit nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB can selectively regulate Abeta42, Abetab42 reduction is not mediated by inhibition of NF-kappaB activation. Because of its efficacy at lowering Abeta42 production and low toxicity profile, R-flurbiprofen is a strong candidate for clinical development.
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