Group IIA secretory phospholipase A2 (sPLA2-IIA)

Group IIA secretory phospholipase A2 (sPLA2-IIA), encoded by the PLA2G2A gene, is a low-molecular-weight enzyme that catalyzes the hydrolysis of the sn-2 ester bond of phospholipids to release free fatty acids and lysophospholipids. It plays a critical role in the propagation of inflammatory responses by providing arachidonic acid for the synthesis of eicosanoids and has been implicated in the pathogenesis of various inflammatory diseases, including sepsis, rheumatoid arthritis, and cardiovascular disorders. In oncology, sPLA2-IIA is often overexpressed in tumors such as lung and prostate cancer, where it promotes cell proliferation, invasion, and resistance to apoptosis, particularly in the context of K-ras mutations. Therapeutic targeting of sPLA2-IIA has primarily focused on small-molecule inhibitors like varespladib, which aim to dampen systemic inflammation and inhibit tumor progression. While clinical trials for sepsis and acute coronary syndrome have faced challenges, sPLA2-IIA remains a significant target for precision medicine, especially as a biomarker for patient stratification in cancer and as a potential treatment for snakebite envenomation due to its structural homology with venom toxins. The enzyme's dual role as a pro-inflammatory mediator and a potent antimicrobial agent highlights its complex biological function in the human innate immune system.

Other names

PLA2G2APhosphatidylcholine 2-acylhydrolase 2ANon-pancreatic secretory phospholipase A2Group IIa sPLA2GIIC sPLA2

Inhibition of sPLA2-IIA enzymatic activity, preventing the hydrolysis of phospholipids and the subsequent release of pro-inflammatory mediators like arachidonic acid.