The role of intracellular anionic phospholipids in the production of N-acyl-phosphatidylethanolamines by cytosolic phospholipase A2ɛ

PLA2G4E, a candidate gene for resilience in Alzheimer´s disease and a new target for dementia treatment

“…The mechanism underlying the cognitive improvement associated with PLA2G4E expression may involve an increase in the number of dendritic spines, which is independent of the pathological changes in amyloid and tau. The results obtained are in agreement with earlier data whereby the treatment with phosphatidylserine, a phospholipid that activates PLA2G4E (Binte Mustafiz et al, 2019), improved memory deficits in AD rats and patients (Zhang et al, 2015).. Moreover, PLA2G4E was recently described as the calcium-dependent N-acyltransferase that produces N-acyl phosphatidylethanolamines (NAPEs), precursors of N-acyl ethanolamine (NAE) and lipid transmitters like the endocannabinoid anandamide (Ogura et al, 2016).…”

Updating Phospholipase A2 Biology

“…In response to Ca 2+ ionophore stimulation, HEK293 cells overexpressing cPLA 2 ε produce various NAPE and NAE species, accompanied by concomitant decreases in PE and PC and increases in LPE and LPC, indicating that cPLA 2 ε produces NAPEs by utilizing the diacyl- and plasmalogen types of PE as acyl acceptors and the diacyl types of PC and PE as acyl donors [ 103 ] ( Figure 4 A). The activity of cPLA 2 ε is markedly enhanced by the presence of phosphatidylserine (PS) or other anionic phospholipids, and cPLA 2 ε largely co-localizes with PS in the plasma membrane and organelles involved in the endocytic pathway [ 104 , 105 ]. This localization might be related to the observation that cPLA 2 ε drives recycling through the clathrin-independent endocytic route [ 106 ].…”