The key roles of reactive oxygen species in microglial inflammatory activation: Regulation by endogenous antioxidant system and exogenous sulfur-containing compounds

Aberrant innate immunity in the brain has been implicated in the pathogenesis of several central nervous system (CNS) disorders, including Alzheimer's disease, Huntington's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, and depression. Except for extraparenchymal CNS-associated macrophages, which predominantly afford protection against peripheral invading pathogens, it has been reported that microglia, a population of macrophage-like cells governing CNS immune defense in nearly all neurological diseases, are the main CNS resident immune cells. Although microglia have been recognized as the most important source of reactive oxygen species (ROS) in the CNS, ROS also may underlie microglial functions, especially M1 polarization, by modulating redox-sensitive signaling pathways. Recently, endogenous antioxidant systems, including glutathione, hydrogen sulfide, superoxide dismutase, and methionine sulfoxide reductase A, were found to be involved in regulating microglia-mediated neuroinflammation. A series of natural sulfur-containing compounds, including S-adenosyl methionine, S-methyl-L-cysteine, sulforaphane, DMS, and S-alk(enyl)-l-cysteine sulfoxide, modulating endogenous antioxidant systems have been discovered. We have summarized the current knowledge on the involvement of endogenous antioxidant systems in regulating microglial inflammatory activation and the effects of sulfurcontaining compounds on endogenous antioxidant systems. Finally, we discuss the possibilities associated with compounds targeting the endogenous antioxidant system to treat neuroinflammation-associated diseases.

Automated summary

Aberrant innate immunity in the brain is associated with several CNS disorders. Microglia, the main immune cells in the CNS, and endogenous antioxidant systems play important roles in regulating neuroinflammation. Sulfur-containing compounds that modulate these systems may have therapeutic potential for neuroinflammation-related diseases.