Journal
CURRENT OPINION IN NEUROLOGY
Volume 22, Issue 3, Pages 308-314Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/WCO.0b013e32832a3225
Keywords
heme oxygenase-1; microglia; neurodegenerative diseases; NFkappaB; Nrf2
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Funding
- Spanish Ministry of Science and Innovation [SAF2007-62646]
- FPU from Universidad Autonoma of Madrid.
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Purpose of review This review discusses some of the emerging concepts on how modulation of redox homeostasis in microglia is crucial to restore its inactive state and modulate inflammation in neurologic diseases. Recent findings Reactive oxygen species generated by microglia help to eliminate pathogens in the extracellular milieu but also act on microglia itself, altering the intracellular redox balance and functioning as second messengers in induction of proinflammatory genes. Recent findings indicate that restoration of redox balance may be determinant in driving microglia back to the resting state. Thus, deficiency of the transcription factor NF-E2-related factor-2 (Nrf2), guardian of redox homeostasis, results in exacerbated inflammatory response to neurotoxins whereas inducers of Nrf2 and its target heme oxygenase-1 downmodulate inflammation. Summary New available information indicates that downregulation of microglia is a matter closely correlated with control of oxidative stress in this cell type and points to Nrf2 as a new therapeutic target for modulation of inflammation in neurodegenerative diseases.
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