Sun GY, Horrocks LA, Farooqui AAThe roles of NADPH oxidase and phospholipases A2 in oxidative and inflammatory responses in neurodegenerative diseases. J Neurochem 103:1-16

Department of Biochemistry, University of Missouri, Columbia, Missouri, USA.
Journal of Neurochemistry (Impact Factor: 4.28). 11/2007; 103(1):1-16. DOI: 10.1111/j.1471-4159.2007.04670.x
Source: PubMed


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 Ca(2+)-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 A(2) (PLA(2)). This review is intended to cover recent studies describing ROS generation from NADPH oxidase in the CNS and its downstream activation of PLA(2), namely, the group IV cytosolic cPLA(2) and the group II secretory sPLA(2). A major focus is to elaborate the dual role of NADPH oxidase and PLA(2) in 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 PLA(2) will 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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Available from: Grace Sun, Apr 10, 2014
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    • "Microglia derived inflammatory cytokines are capable of binding astrocytic cytokine receptors that are coupled to cytosolic phospholipase A2 (cPLA2), and secretory phospholipase A2 (sPLA2) [122]. Activation of these Ca2+-dependent enzymes results in the hydrolysis of membrane phospholipids, liberating arachidonic acid (AA) [123,124], itself a precursor of pro-inflammatory eicosanoids including prostaglandins and leukotrienes [125,126]. "
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    • "These types of inflammatory reactions are stressors for neurons and will be adding to oxidative stress that neurons are subject to. All these in turn will be damaging to mitochondria and other cellular organelles which may lead to further inflammatory reactions in neurons and other cells in CNS (see review by Sun et al. [11]). A key molecule regulating the cellular antioxidant response is the basic region leucine-zipper transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). "
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