Activity of flurbiprofen and chemically related anti-inflammatory drugs in models of Alzheimer's disease

Laura Gasparini, Ennio Ongini, Donna Wilcock, David Morgan

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Currently, there is an intense debate on the potential use of nonsteroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease (AD). NSAIDs are among the most widely prescribed drugs for the treatment of pain, fever, and inflammation. Their effects are largely attributed to the inhibition of the enzymatic activity of cyclooxygenase (COX)-1 and -2. The apparent activity of this class of drugs stems from one critical pathological process underlying AD and other neurodegenerative disorders, i.e., the presence of chronic neuroinflammation. In fact, prolonged use of NSAIDs is associated with reduced risk of AD. Besides COX inhibition, additional mechanisms could contribute to the potential activity of NSAIDs in AD. For example, several studies show that only a few selected NSAIDs also affect β-amyloid (Aβ) deposition and metabolism. Among the Aβ-effective NSAIDs, flurbiprofen raised particular interest because of its multiple actions on key AD hallmarks. Studies in cell lines and animal models have shown that flurbiprofen racemate, its R-enantiomer and its nitric oxide (NO)-releasing derivatives, HCT 1026 and NCX 2216, are effective on AD amyloid pathology. Moreover, HCT 1026 and NCX 2216 differentially influence the cellular component of neuroinflammation (i.e., microglia activation) in some experimental settings, i.e., HCT 1026 inhibits the activation of microglia, while NCX 2216 can either enhance or inhibit microglial activation, depending upon the experimental conditions. It is still unclear which effects on microglia will prove most beneficial. Ultimately, clinical studies in AD patients will provide the best information as to whether selected NSAIDs will improve this devastating disease.

Original languageEnglish
Pages (from-to)400-408
Number of pages9
JournalBrain Research Reviews
Volume48
Issue number2
DOIs
StatePublished - Apr 2005

Bibliographical note

Funding Information:
Portions of this work were supported by AG18478 and AG 15490 to DM. DW is the Benjamin fellow for Alzheimer's research.

Keywords

  • Alzheimer's disease
  • Flurbiprofen
  • HCT 1026
  • Microglia
  • NCX 2216
  • NSAIDs

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology

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