Inhibitors of intracellular phospholipase A2 activity: their neurochemical effects and therapeutical importance for neurological disorders.
Intracellular phospholipases A2 (PLA2) are a diverse group of enzymes with a growing number of members. These enzymes hydrolyze membrane phospholipids 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 PLA2 have been recently discovered. However, nothing is known about their neurochemical effects, mechanism of action or toxicity in human or animal models of neurological disorders. Elevated intracellular PLA2 activities, found in neurological disorders 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 PLA2 that can cross blood-brain barrier without harm. Currently, potent intracellular PLA2 inhibitors are not available for clinical use in human or animal models of neurological disorders, but studies on this interesting topic are beginning to emerge. The use of nonspecific intracellular PLA2 inhibitors (quinacrine, heparin, gangliosides, vitamin E) in animal model studies of neurological disorders in vivo has provided some useful information on tolerance, toxicity, and effectiveness of these compounds.
Farooqui
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AA
Department of Medical Biochemistry, The Ohio State University, Columbus 43210, USA. farooqui.l@osu.edu
Litsky
M L
ML
Farooqui
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T
Horrocks
L A
LA
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002240:Carbohydrate Sequence; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000201:enzymology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010741:Phospholipases A; D054467:Phospholipases A2