[The role of cyclooxygenases in neurotoxicity of amyloid beta peptides in Alzheimer's disease].
In the course of Alzheimer's disease (AD), chronic inflammation is initiated by amyloid beta (Ab) 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 Ab 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 Ab 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.
Cakała
Magdalena
M
Zakład Komórkowej Transdukcji Sygnału, Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego PAN, ul. Pawińskiego 5, 02-106 Warszawa, Poland.
Strosznajder
Joanna B
JB
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D000682:Amyloid / Q000187:drug effects; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases