Cytosolic Phospholipase A2 Inhibitors as Therapeutic Agents for Neural Cell Injury
A. A. Farooqui,
X.- R. Lu,
L. A. Horrocks.
Cytosolic phospholipases A2 are a diverse group of enzymes with a growing number of members. These enzymes hydrolyze membrane glycerophospholipids into arachidonic acid and 1-acyl-lysophospholipids. Arachidonic acid and its metabolites (eicosanoids) play critical roles in the initiation and modulation of inflammation and oxidative stress. It is generally thought that the release of arachidonic acid by cytosolic phospholipase A2 is the rate-limiting step in the generation of eicosanoids. Neurological disorders, such as ischemia, spinal cord injury, and Alzheimers disease, are characterized by inflammatory reactions, oxidative stress, and increased cytosolic phospholipase A2 activity. Several cytosolic phospholipase A2 inhibitors were discovered recently. However, nothing is known about their neurochemical effects, mechanism of action, or toxicity in human or animal models of neurological disorders. Our recent studies have indicated that the use of cytosolic PLA2 inhibitors in kainic acid-induced toxicity model of neural injury can provide useful information on the beneficial effects of these compounds in brain tissue.
Keywords: Cytosolic, Phospholipase, A2 Inhibitors, Neural Cell, eicosanoids, kainic acid, PLA2 inhibitors, neurochemical
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