Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases

J Lipid Res. 2004 Feb;45(2):205-13. doi: 10.1194/jlr.R300016-JLR200. Epub 2003 Dec 1.

Abstract

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 Ca(2+)-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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / enzymology*
  • Animals
  • Astrocytes / metabolism
  • Brain Ischemia / enzymology*
  • Calcium / metabolism
  • Cell Differentiation / physiology
  • Central Nervous System / cytology
  • Central Nervous System / enzymology*
  • Eicosanoic Acids / metabolism*
  • Humans
  • Inflammation / metabolism
  • Mice
  • Neurodegenerative Diseases / enzymology*
  • Neurons / metabolism
  • Oxidative Stress / physiology
  • Phospholipases A / metabolism*
  • Phospholipases A2
  • Phospholipids / metabolism
  • Signal Transduction / physiology

Substances

  • Eicosanoic Acids
  • Phospholipids
  • Phospholipases A
  • Phospholipases A2
  • arachidic acid
  • Calcium