Inhibition of phospholipase A2 as a therapeutic target

The hydrolysis of cell membrane phospholipids by phospholipase A2 (PLA2) leads to the production of numerous lipid mediators of diverse pathological conditions, mainly inflammatory diseases. These include lysophospholipids and their derivatives, and arachidonic acid and its derivatives (the eicosanoids). Both these groups of mediators are produced predominantly by the secretory PLA2s (sPLA2s) which hydrolyze the phospholipids of the cell surface membrane. Protection of cell membrane from these ‘inflammatory enzymes’ can therefore be used for the treatment of inflammatory processes. A prototype of cell-impermeable PLA2 inhibitors, which protect the cell membrane from different sPLA2s without affecting vital phospholipid metabolism, is presented and discussed in the present review.