Potential therapeutic uses of phospholipase A2 inhibitors

The cleavage of the sn-2 ester of membrane phospholipids by phospholipase A(2) has long been ascribed as the important initiation step in the production of proinflammatory mediators, including prostaglandins, leukotrienes and platelet-activating factor. Consequently, this enzymatic action has been implicated in the pathogenesis of a multitude of diseases, ranging from lung inflammation and arthritis to neural injuries and cardiovascular disease. The three types of phospholipase A(2) that have received the most research attention are: secretory phospholipase A(2) (sPLA(2)), cytosolic phospholipase A(2) (cPLA(2)) and lipoprotein-associated phospholipase A(2) (LpPLA(2)). This review will discuss the likely roles of these PLA(2) in the development of the disease conditions and recent advances in the development of specific inhibitors, based on the patent literature from December 2000 to December 2003.