Maintenance of synaptic stability requires calcium-independent phospholipase A₂ activity

Phospholipases A₂ (PLA₂s) represent one of the largest groups of lipid-modifying enzymes. Over the years, significant advances have been made in understanding their potential physiological and pathological functions. Depending on their calcium requirement for activation, PLA₂s are classified into calcium dependent and independent. This paper mainly focuses on brain calcium-independent PLA₂ (iPLA₂) and on the mechanisms by which they influence neuronal function and regulate synaptic plasticity. Particular attention will be given to the iPLA₂γ isoform and its role in the regulation of synaptic glutamate receptors. In particular, the paper discusses the possibility that brain iPLA₂γ deficiencies could destabilise normal synaptic operation and might contribute to the aetiology of some brain disorders. In this line, the paper presents new data indicating that iPLA₂γ deficiencies accentuate AMPA receptor destabilization and tau phosphorylation, which suggests that this iPLA₂ isoform should be considered as a potential target for the treatment of Tau-related disorders.