Journal
FASEB JOURNAL
Volume 19, Issue 12, Pages 1592-1601Publisher
WILEY
DOI: 10.1096/fj.04-3620rev
Keywords
amyloid beta; APP metabolism; inflammation; central nervous system; NSAIDs; cyclooxygenase; coxibs
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Funding
- NIA NIH HHS [AG-11542, AG-22512] Funding Source: Medline
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Alzheimer's disease (AD) is the most common form of neurodegenerative disorder with dementia in the elderly. The AD brain pathology is characterized by deposits of amyloid-beta (A beta) peptides and neurofibrillary tangles but also (among other aspects) by signs of a chronic inflammatory process. Epidemiological studies have shown that long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD and delays its onset. Classical targets of NSAIDs include cycloxygenase, nuclear factor kappa B, and peroxisome proliferator-activated receptors. Modulation of these pathways, all of which have been implicated in AD pathogenesis, could explain the NSAID effect on AD progression. However, recent studies indicate that a subset of NSAIDs such as ibuprofen, indomethacin, and flurbiprofen may have direct A beta-lowering properties in cell cultures as well as transgenic models of AD-like amyloidosis. A renewed interest in the old and a discovery of new pharmacological properties of these drugs are providing vital insight for future clinical trials. In this review we will summarize how the combination of traditional (anti-inflammatory) and new (anti-amyloidogenic) properties of some NSAIDs is providing unprecedented opportunities for drug discovery and could potentially result in novel therapeutic approaches for the treatment of AD.
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