Cytosolic phospholipase A2 group IVA (cPLA2α) (cPLA2α)

Cytosolic phospholipase A2 group IVA (cPLA2α) is a key enzyme in neutrophils that catalyzes the hydrolysis of membrane phospholipids at the sn-2 position to release arachidonic acid [1, 2]. This enzymatic activity is the rate-limiting step for the production of eicosanoids, such as prostaglandins and leukotrienes, which are central mediators of the inflammatory response [2, 5]. In neutrophils, cPLA2α is activated by increased intracellular calcium levels and phosphorylation by mitogen-activated protein kinases (MAPKs), leading to its translocation to intracellular membranes [1, 3]. Beyond its role in lipid mediator synthesis, cPLA2α is involved in the activation of the NADPH oxidase complex, which is essential for the neutrophil respiratory burst and pathogen killing [3]. Overactivity of this enzyme is associated with chronic inflammatory diseases, including rheumatoid arthritis, asthma, and acute respiratory distress syndrome [2, 5]. Therapeutic strategies have focused on developing small-molecule inhibitors of cPLA2α to reduce systemic and local inflammation [4]. While several inhibitors like efipladib have been investigated in clinical trials, challenges remain regarding their efficacy and safety profiles in human patients [4]. Monitoring biomarkers such as leukotriene B4 and prostaglandin E2 levels can help assess the pharmacodynamic effect of these inhibitors [2].

Other names

PLA2G4APhospholipase A2 group IVAcPLA2-alphaCalcium-dependent phospholipid-binding protein

Inhibition of the enzymatic hydrolysis of the sn-2 ester bond of phospholipids, preventing the release of arachidonic acid and subsequent eicosanoid production.