The genetics of phospholipase A2 induced redox signaling in neuroinflammation and neuronal diseases

The brain is the most metabolically active organ, consumes the most oxygen in the body, and also produces excess RSM (reactive signaling molecules). RSMs induce diverse inflammatory mediators (IM) in astrocytes and neuroglia that activate phospholipase A2 (PLA2), which catalyzes platelet activating factor (PAF) to release arachidonic acid (AA). AA activates cyclooxygenase (COX), lipoxygenase (LOX), and p450 cytochrome pathways to generate further RSM. This increased oxidative stress leads to lipid peroxidation (LPO) and protein oxidation, resulting in neuroinflammation and neurodegeneration. RSM-mediated excess IM alters intracellular signaling cascades in neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and multiple sclerosis (MS). Numerous genes have been identified that are associated with neurodegenerative diseases, most of which are involved in the PLA2-ROS (reactive oxygen species) pathway. Thus, PLA2-ROS pathway genes would be extremely useful to identify therapeutic targets to treat cognitive decline, and the development of pathologic symptoms in these debilitating neuronal diseases.