Znaczenie cyklooksygenaz w neurotoksyczności peptydów amyloidu β w chorobie Alzheimera

In the course of Alzheimer's disease (AD), chronic inflammation is initiated by amyloid β (Aβ) peptide aggregates that extensively participate in neurodegeneration. Epidemiological studies have shown that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD. NSAIDs are inhibitors of cyclooxygenases (COXs), enzymes involved in synthesis of eicosanoids, a major component of the inflammatory process. Recent studies have brought two new findings: 1) the toxic form of Aβ is its intra- and extracellular oligomers, rather than aggregates; 2) COX-2 activation is an early event in AD, preceding plaque formation and microglia activation. This finding suggests that COX might participate in Aβ toxicity in neurons in the early stage of AD independently of its role in the inflammatory reaction in glial cells in the advanced stage of AD. However, further studies on the role of COXs in the pathogenesis/pathomechanism of AD are needed.