The role of phospholipase A2 in multiple Sclerosis: A systematic review and meta-analysis

Phospholipases A2 (PLA₂) are a diverse group of enzymes that cleave the fatty acids of membrane phospholipids. They play critical roles in pathogenesis of neurodegenerative diseases such as multiple sclerosis by enhancing oxidative stress and initiating inflammation. The levels of PLA₂ activity in MS patients compared to controls and role of inhibiting PLA₂ activity on severity scores in different experimental models are not comprehensively assessed in the light of varying evidence from published studies. The objective of this systematic review is to determine the association between PLA₂ activity and multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). We performed a systematic review of six studies that assessed PLA₂ activity in MS patients compared to controls and nine studies that assessed PLA₂ activity in EAE. sPLA₂ nor Lp-PLA₂ activity were not increased in MS compared to controls in five of those six studies. A difference in sPLA₂ activity was only found in a study that measured the enzyme activity in urine. However, inhibiting cPLA₂ or sPLA₂ led to lower clinical severity or no signs of EAE in mice, and a lower incidence of EAE lesions compared to animals without cPLA₂ inhibition. These findings indicate that PLA₂ appears to play a role in the pathogenesis of EAE.