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

Phospholipase A(2) (PLA(2)) 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 PLA(2) in the mammalian system, but recent studies have focused on three major groups, namely, the group IV cytosolic PLA(2), the group II secretory PLA(2) (sPLA(2)), and the group VI Ca2+-independent PLA(2). These PLA(2)s 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. PLA(2)s acting on membrane phospholipids have been implicated in intracellular membrane trafficking, differentiation, proliferation, and apoptotic processes. All major groups of PLA(2) are present in the central nervous system (CNS). Therefore, this review is focused on PLA(2) 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 PLA(2) 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 PLA(2) in regulating physiological and pathological functions in the CNS.