Nadia G Innamorato1, Isabel Lastres-Becker, Antonio Cuadrado. 1. Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Investigaciones Biomédicas Alberto Sols UAM-CSIC and Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Abstract
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.
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.
Authors: Bárbara Tagliari; Ana Paula Tagliari; Felipe Schmitz; Aline A da Cunha; Carla Dalmaz; Angela T S Wyse Journal: Neurochem Res Date: 2010-12-24 Impact factor: 3.996