engleski

Redox control of microglial function: molecular mechanisms and functional significance

Neurodegenerative diseases are characterized by chronic microglial over-activation and oxidative stress. Both events are tightly linked with neuron damage and it is now beginning to be recognized that reactive oxygen species (ROS) produced by either microglia itself or by the surrounding environment not only impact on neurons but also modulate microglial activity. In this review, we first analyze the hallmarks of pro-inflammatory and anti-inflammatory phenotypes of microglia and its regulation by ROS. Then, we consider the production of reactive oxygen and nitrogen species by NADPH oxidases and nitric oxide synthases and the new findings indicating an essential role of glutathione in redox homeostasis of microglia. The signaling effect of oxidant modification of macromolecules is analyzed in detail at the level of oxidized lipid by-products and sulfhydryl modification of microglial proteins. Redox signaling has a profound impact on two transcription factors that modulate microglial fate, NF-κB and NRF2, master regulators of the pro-inflammatory and antioxidant responses of microglia, respectively. The relevance of these two proteins in modulation of microglial activity and the interplay between them will be discussed. Finally, the relevance of ROS in alteration of blood brain barrier permeability is discussed. Recent examples on the relevance of these findings on the onset or progression of neurodegenerative diseases are also discussed. This review should provide a deep view of the role of redox homeostasis in microglial activity and help in the identification of new and promising targets to control neuroinflammation through redox control of the brain.

microglia; redox control; ROS; neuroinflammation

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