ABSTRACT
Microglial cells are the neuroprotective immunocompetent cells in the central nervous system and have important functions in the normal as well as in the injured and inamed brain.1-4 In the healthy brain, microglial cells perform a continuous active tissue scanning for an altered microenvironment.5 If this environment is disturbed, microglial cells respond with a program of protective activities that are part of the innate defense mechanisms of the brain and assist in specic immune functions and repair processes. After this activation, microglial cells produce and release a large number of neuroactive substances that include various cytokines, prostanoids, and proteases as well as radicals such as nitric oxide and superoxide.1,2,6 Microglial activation primarily aims at the protection of the brain, since microglia-derived compounds contribute to the defense of the brain against pathogens and are important for the stimulation of repair processes after brain damage. Superoxide and NO support the cellular defense but have also the potential to harm the reactive oxygen species (ROS)-producing cell as well as neighboring cells. In addition, inappropriate activation can lead
27.1 Introduction .......................................................................................................................... 393 27.2 Generation of Reactive Oxygen Species by Microglial Cells .............................................. 394 27.3 Antioxidative Defense in Microglial Cells ........................................................................... 394
27.3.1 Low Molecular Weight Antioxidants in Microglial Cells ........................................ 395 27.3.2 Antioxidative Enzymes in Microglial Cells ............................................................. 396
27.3.2.1 Superoxide Dismutase................................................................................ 396 27.3.2.2 Glutathione Peroxidase .............................................................................. 396 27.3.2.3 Glutathione Reductase ............................................................................... 397 27.3.2.4 Catalase ...................................................................................................... 397 27.3.2.5 NADPH Regenerating Enzymes ................................................................ 397 27.3.2.6 Other Enzymes .......................................................................................... 398
27.4 Peroxide Metabolism ............................................................................................................ 398 27.5 Summary .............................................................................................................................. 398 Acknowledgments .......................................................................................................................... 398 References ...................................................................................................................................... 399
to cell degeneration. A variety of neurotoxins have been reported to cause neurotoxicity through the ROS that are generated by microglial nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase (Nox).2 Therefore, microglial cells have also been considered as the enemy within the brain that is harmful for other brain cells due to the release of inammatory cytokines and toxic ROS. The various aspects of microglial functions and dysfunctions for physiological and pathological situations in brain as well as the potential of microglial cells as pharmacological target for diseases have recently been reviewed in detail.1-4,7-9 Here we will focus on the antioxidative potential of microglial cells that contributes to the self-defense of microglial cells against the ROS that these cells produce after activation.
