Cytosolic phospholipase A2 (cPLA2)-mediated oxidative and inflammatory responses in neurodegenerative diseases

Neurodegenerative diseases are increasing globally in parallel with modernization, changes in lifestyle, and aging populations. Understanding the etiology of the disease and the function of each biological factor that contributes to it is crucial for effective treatment. cPLA2, being a critical enzyme, intermediates the oxidative stress and inflammatory responses in several neurodegenerative diseases. In addition to mediating neurodegenerative diseases, cPLA2 itself may also have a role in modifying membrane physical characteristics, altering membrane trafficking, glucose metabolism, platelet activation, memory and cognitive function, ovulation, and regulating some reproductive processes. The growing interest in cPLA2 is due to its hydrolysis at sn-2 position, which releases arachidonic acid (AA), the substrate for the catalytic action of cyclooxygenases and lipoxygenases. Low calcium level activates cPLA2 and controls receptor-mediated eicosanoid production. The dependency on calcium at C2 domain, as well as the proclivity to go through several posttranslational changes, such as s-nitrosylation, and phosphorylation, contributes to the enzyme's unique catalysis. This review briefly emphasizes the function of cPLA2 in different neurodegenerative diseases, including AD, PD, and MS, and the signaling pathways involved in the cPLA2-mediated oxidative and inflammatory responses in different cells of CNS.