K. Townsend, D. Praticò
Oct 1, 2005
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6
Influential Citations
204
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Journal
The FASEB Journal
Abstract
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‐β (Aβ) 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 κB, 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 Aβ‐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. Townsend K. P., Praticò D. Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti‐inflammatory drugs. FASEB J. 19, 1592–1601 (2005)