In the present study, we used immunohistochemistry and Western blotting to investigate the involvement of PLA2G6 in Lewy body disease (PD and DLB), multiple system atrophy and Alzheimer's disease, in comparison with normal controls.
Thus, the present data suggest that PS2 mutations suppress lung tumor development by inhibiting the iPLA2 activity of PRDX6 via a γ-secretase cleavage mechanism and may explain the inverse relationship between cancer and AD incidence.
Investigating the metabolic and signaling pathways involving Abeta NADPH oxidase and PLA(2) can help understand the mechanisms underlying the neurodegenerative effects of oxidative stress in AD.
Arachidonic acid (AA) and specific isoforms of phospholipase A(2) (PLA(2)) appear to be critical mediators in amyloid-beta (Abeta)-induced pathogenesis, leading to learning, memory, and behavioral impairments in mouse models of AD.
The use of positive modulators of PLA2 (especially of cPLA2 and iPLA2) or supplementation with dietary lipid compounds (e.g., arachidonic acid) in combination with cognitive training could be a valuable therapeutic strategy for cognitive enhancement in early-stage AD.