The roles of NADPH oxidase and phospholipases A2in oxidative and inflammatory responses in neurodegenerative diseases

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Abstract
Reactive oxygen species (ROS) are produced in mammalian cells through enzymic and non‐enzymic mechanisms. Although some ROS production pathways are needed for specific physiological functions, excessive production is detrimental and is regarded as the basis of numerous neurodegenerative diseases. Among enzymes producing superoxide anions, NADPH oxidase is widespread in mammalian cells and is an important source of ROS in mediating physiological and pathological processes in the cardiovascular and the CNS. ROS production is linked to the alteration of intracellular calcium homeostasis, activation of Ca2+‐dependent enzymes, alteration of cytoskeletal proteins, and degradation of membrane glycerophospholipids. There is evolving evidence that ROS produced by NADPH oxidase regulate neuronal functions and degrade membrane phospholipids through activation of phospholipases A2(PLA2). This review is intended to cover recent studies describing ROS generation from NADPH oxidase in the CNS and its downstream activation of PLA2, namely, the group IV cytosolic cPLA2and the group II secretory sPLA2. A major focus is to elaborate the dual role of NADPH oxidase and PLA2in mediating the oxidative and inflammatory responses in neurodegenerative diseases, including cerebral ischemia and Alzheimer’s disease. Elucidation of the signaling pathways linking NADPH oxidase with the multiple forms of PLA2will be important in understanding the oxidative and degradative mechanisms that underline neuronal damage and glial activation and will facilitate development of therapeutic intervention for prevention and treatment of these and other neurodegenerative diseases.

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