Potential therapeutic uses of phospholipase A₂ inhibitors

Abstract

The cleavage of the sn-2 ester of membrane phospholipids by phospholipase A₂ has long been ascribed as the important initiation step in the production of pro-inflammatory 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 A₂ that have received the most research attention are: secretory phospholipase A₂ (sPLA₂), cytosolic phospholipase A₂ (cPLA₂) and lipoprotein-associated phospholipase A₂ (LpPLA₂). This review will discuss the likely roles of these PLA₂ 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.

• arachidonic acid
• arthritis
• asthma
• atherosclerosis
• inflammation
• inhibitors
• neural injuries
• phospholipase A2
• sepsis