ABSTRACT Phospholipases A 2 (PLA 2s) represent one of the largest groups of lipid-modifying enzymes. Remarkable advances have been made during the last decade to understand their potential physiological and pathological implications. Although several PLA 2s become fully activated after calcium mobilization, it appears that, under resting conditions, several cell types maintain a high level of PLA 2 activity which is, in nature, independent of calcium variations. This review will mainly focus on the roles of calcium-independent PLA 2 (iPLA 2) enzymes in the brain and on the mechanisms by which they could influence neuronal function and integrity. Particular attention will be given to how the iPLA2 isoform can control both the biochemical and functional properties of glutamate receptors and, consequently, synaptic plasticity and glutamate-induced excitotoxic cell damage. In this line, we will finally discuss the possibility that brain iPLA2 deficiencies can contribute to the appearance of brain disorders through mechanisms involving tau phosphorylation and mitochondrial dysfunction.
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