Brain Cytosolic Phospholipase A2: Localization,Role,and Involvement in Neurological Diseases

Abstract

Cytosolic phospholipase A₂ (cPLA₂) hydrolyzes the arachidonoyl group from the sn-2 position of glycerophospholipids generating arachidonic acid and lysophospholipids. The products of the cPLA₂-catalyzed reaction act as second messengers themselves or further metabolize to eicosanoids, platelet activating factor, and lysophosphatidic acid. cPLA₂ has not been purified from brain tissue. Immunocytochemical studies have indicated that cPLA₂ is expressed in neurons and astrocytes. The hindbrain and spinal cord contain dense immunoreactivity for cPLA₂. Activity and immunoreactivity of cPLA₂ are markedly increased in ischemia, Alzheimer’s disease, and kainic acid neurotoxicity. This increase in cPLA₂ activity and immunoreactivity is accompanied by marked alterations in neural membrane phospholipid composition and the accumulation of lipid peroxides and eicosanoids. At present, it is not known whether the increased activity and immunoreactivity of cPLA₂ in neural trauma (e.g., in ischemia) and neurodegenerative disease (Alzheimer’s disease) is the cause or effect of neurodegeneration. Recent studies on the role of this enzyme in brain tissue suggest that cPLA₂ may be involved in synaptic plasticity, generation of second messengers, axon regeneration, and neurodegeneration.