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-kappaB, 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.
Lleo
A
A
Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Galea
E
E
Sastre
M
M
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D047495:PPAR gamma; D011451:Prostaglandin-Endoperoxide Synthases; D053829:Amyloid Precursor Protein Secretases; D020741:rho GTP-Binding Proteins