The emerging role of group VI calcium-independent phospholipase A2 in releasing docosahexaenoic acid from brain phospholipids

Brain phospholipids are highly enriched in docosahexaenoic acid (DHA; 22:6n-3). Recent advances indicate that 22:6n-3 is released from brain phospholipids via the action of phospholipase A(2) (PLA(2)) in response to several stimuli, including neurotransmission, where it then acts as a secondary messenger. Furthermore, it is now known that released 22:6n-3 is a substrate for several oxygenation enzymes whose products are potent signaling molecules. One emerging candidate PLA(2) involved in the release of 22:6n-3 from brain phospholipids is the group VI calcium-independent phospholipase A(2) (iPLA(2)). After a brief review of brain 22:6n-3 metabolism, cell culture and rodent studies facilitating the hypothesis that group VI iPLA(2) releases 22:6n-3 from brain phospholipids are discussed. The identification of PLA(2)s involved in cleaving 22:6n-3 from brain phospholipids could lead to the development of novel therapeutics for brain disorders in which 22:6n-3 signaling is disordered.