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Journal of Lipid Research, Vol. 45, 205-213, February 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Thematic Review

Phospholipase A₂ in the central nervous system

Grace Y. Sun², Jianfeng Xu¹, Michael D. Jensen and Agnes Simonyi

Department of Biochemistry, University of Missouri, Columbia, MO 65211

² To whom correspondence should be addressed. e-mail: sung{at}health.missouri.edu

Phospholipase A₂ (PLA₂) belongs to a family of enzymes that catalyze the cleavage of fatty acids from the sn-2 position of phospholipids. There are more than 19 different isoforms of PLA₂ in the mammalian system, but recent studies have focused on three major groups, namely, the group IV cytosolic PLA₂, the group II secretory PLA₂ (sPLA₂), and the group VI Ca²⁺-independent PLA₂. These PLA₂s are involved in a complex network of signaling pathways that link receptor agonists, oxidative agents, and proinflammatory cytokines to the release of arachidonic acid (AA) and the synthesis of eicosanoids. PLA₂s acting on membrane phospholipids have been implicated in intracellular membrane trafficking, differentiation, proliferation, and apoptotic processes. All major groups of PLA₂ are present in the central nervous system (CNS). Therefore, this review is focused on PLA₂ and AA release in neural cells, especially in astrocytes and neurons. In addition, because many neurodegenerative diseases are associated with increased oxidative and inflammatory responses, an attempt was made to include studies on PLA₂ in cerebral ischemia, Alzheimer's disease, and neuronal injury due to excitotoxic agents.

Information from these studies has provided clear evidence for the important role of PLA₂ in regulating physiological and pathological functions in the CNS.

Abbreviations: AA, arachidonic acid; AD, Alzheimer's disease; COX, cyclooxygenase; cPLA₂, cytosolic PLA₂; DHA, docosahexaenoic acid; ERK, extracellular signal-regulated protein kinase; FFA, free fatty acid; IFN, interferon gamma; IL-1ß, interleukin-1ß; iPLA₂, Ca²⁺-independent PLA₂; KA, kainic acid; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MCA, middle cerebral artery; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NMDA, N-methyl-D-aspartic acid; PE, phosphatidylethanolamine; PE_pl, ethanolamine plasmalogen; PGE2, prostaglandin E2; PLA₂, phospholipase A₂; ROS, reactive oxygen species; sPLA₂, secretory PLA₂; TNF, tumor necrosis factor alpha

Supplementary key words astrocytes • neurons • neurodegeneration • Alzheimer's disease • cerebral ischemia

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