Role of cytosolic Calcium-dependent Phospholipase A2 in Alzheimer’s disease pathogenesis

Phospholipases (PLA2s) are a super family of enzymes characterized by the ability to specifically hydrolyze the sn-2 ester bond of phospholipids generating arachidonic acid, utilized in inflammatory responses and lysophospholipids involved in the control of cell membrane remodeling and fluidity. PLA2s have been so far considered a crucial element in the etiopathogenesis of several neurological diseases such as cerebral ischemia, multiple sclerosis, Parkinson disease and Alzheimer’s disease (AD). In AD the role of β-amyloid (Aβ) fragments is well-established although still more elusive are the molecular events of the cascade that from the Aβ accumulation leads to neurodegeneration with its clinical manifestations. However, it is well-known that inflammation and alteration of lipid metabolism are common features of AD brains. Findings obtained from in vitro studies, animal models and human brain imaging analysis point towards PLA2 as a key molecule in the onset and maintenance of the neurodegenerative mechanism(s) of AD. In this review we have focused on the molecular and biological evidence of the involvement of PLA2s in the pathogenesis of AD. An insight into the molecular mechanism(s) underlying the action and the regulation of PLA2 is of tremendous interest in the pharmaceutical and biotechnology industry in developing selective and potent inhibitors able to modulate the onset and/or the outcome of AD.