Positive and negative effects of prostaglandins in Alzheimer's disease

Abstract

The aim of this review was to clarify the role of prostaglandins and prostaglandin receptors in the immunopathology of Alzheimer's disease. A PubMed search was done using the key word, 'Alzheimer's disease' in combination with the term 'prostaglandins'. Articles from the past 10 years were preferentially selected but important ones from the past 20 years were also included according to the authors' judgment. Alzheimer's disease is characterized by pathological hallmarks such as extracellular deposition of the amyloid β-peptide, the appearance of intracellular neurofibrillary tangles, extensive neuronal loss and synaptic changes in the cerebral cortex and hippocampus. These processes induce inflammatory pathways by activating microglia, astrocytes and infiltrating leukocytes that produce inflammatory mediators including cytokines and prostaglandins.Prostaglandins are small lipid mediators derived from arachidonic acid by multi-enzymatic pathways in which cyclooxygenases and phospholipases are the rate-limiting enzymes. In the central nervous system, prostaglandins exhibit either neurotoxic or neuroprotective effects by acting on specific G-protein-coupled receptors that have different subfamilies and differences in their selective agonists, tissue distribution and signal transduction cascades. Further studies on the role of prostaglandins in Alzheimer's disease may contribute to clarification of their neuroprotective actions, which may lead to the development of successful therapeutic strategies.