Brain phospholipases A2: a perspective on the history.

The phospholipases A2 (PLA2) belong to a large family of enzymes involved in the generation of several second messengers that play an important role in signal transduction processes associated with normal brain function. The phospholipase A2 family includes secretory phospholipase A2, cytosolic phospholipase A2, calcium-independent phospholipase A2, plasmalogen-selective phospholipase A2 and many other enzymes with phospholipase A2 activity that have not been classified. Few attempts have been made purify and characterize the multiple forms of PLA2 and none have been fully characterized and cloned from brain tissue. A tight regulation of phospholipase A2 isozymes is necessary for maintaining physiological levels of free fatty acids including arachidonic acid and its metabolites in the various types of neural cells. Under normal conditions, phospholipase A2 isozymes may be involved in neurotransmitter release, long-term potentiation, growth and differentiation, and membrane repair. Under pathological conditions, high levels of lipid metabolites generated by phospholipase A2 are involved in neuroinflammation, oxidative stress, and neural cell injury.