Inhibitors of intracellular phospholipase A(2) activity: Their neurochemical effects and therapeutical importance for neurological disorders

Intracellular phospholipases A(2) (PLA(2)) are a diverse group of enzymes w ith a growing number of members. These enzymes hydrolyze membrane phospholi pids into fatty acid and lysophospholipids. These lipid products may serve as intracellular second messengers or can be further metabolized to potent inflammatory mediators, such as eicosanoids and platelet-activating factors . Several inhibitors of nonneural intracellular PLA(2) have been recently d iscovered. However, nothing is known about their neurochemical effects, mec hanism of action or toxicity in human or animal models of neurological diso rders. Elevated intracellular PLA(2) activities, found in neurological diso rders strongly associated with inflammation and oxidative stress (ischemia, spinal cord injury, and Alzheimer's disease), can be treated with specific , potent and nontoxic inhibitors of PLA(2) that can cross blood-brain barri er without harm. Currently, potent intracellular PLA(2) inhibitors are not available for clinical use in human or animal models of neurological disord ers, but studies on this interesting topic are beginning to emerge. The use of nonspecific intracellular PLA(2) inhibitors (quinacrine, heparin, gangl iosides, vitamin E) in animal model studies of neurological disorders in vi vo has provided some useful information on tolerance, toxicity, and effecti veness of these compounds. (C) 1999 Elsevier Science Inc.