Molecular targets of non-steroidal anti-inflammatory drugs in neurodegenerative diseases

During the last decade, interest has grown in the beneficial effects of non-steroidal anti-inflammatory drugs (NSAIDs) in neurodegeneration, particularly in pathologies such as Alzheimer’s (AD) and Parkinson’s (PD) disease. Evidence from epidemiological studies has indicated a decreased risk for AD and PD in patients with a history of chronic NSAID use. However, clinical trials with NSAIDs in AD patients have yielded conflicting results, suggesting that these drugs may be beneficial only when used as preventive therapy or in early stages of the disease. NSAIDs may also have salutary effects in other neurodegenerative diseases with an inflammatory component, such as multiple sclerosis and amyotrophic lateral sclerosis. In this review we analyze the molecular (cyclooxygenases, secretases, NF-κB, PPAR, or Rho-GTPasas) and cellular (neurons, microglia, astrocytes or endothelial cells) targets of NSAIDs that may mediate the therapeutic function of these drugs in neurodegeneration.

Authors and Affiliations

1. Department of Neurology, Hospital de la Santa Creu i Sant Pau, 08025, Barcelona, Spain

   A. Lleo

2. Institute of Neurosciences, Autonoma University, and Catalonian Institute for Advanced Studies (ICREA), 08193, Barcelona, Spain

   E. Galea

3. Department of Neurology, University Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

   M. Sastre

Corresponding author

Correspondence to M. Sastre.

Received 4 December 2006; received after revision 24 January 2007; accepted 23 February 2007

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