The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Redox Control of Microglial Function: Molecular Mechanisms and Functional Significance
Open accessAbstract
Neurodegenerative diseases are characterized by chronic microglial over-activation and oxidative stress. It is now beginning to be recognized that reactive oxygen species (ROS) produced by either microglia or the surrounding environment not only impact neurons but also modulate microglial activity. In this review, we first analyze the hallmarks of pro-inflammatory and anti-inflammatory phenotypes of microglia and their 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 that also indicate an essential role of glutathione (γ-glutamyl-l-cysteinylglycine) in redox homeostasis of microglia. The effect of oxidant modification of macromolecules on signaling is analyzed 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, nuclear factor kappa-light-chain-enhancer of activated B cells, and nuclear factor (erythroid-derived 2)-like 2, master regulators of the pro-inflammatory and antioxidant responses of microglia, respectively. The relevance of these proteins in the modulation of microglial activity and the interplay between them will be evaluated. Finally, the relevance of ROS in altering blood brain barrier permeability is discussed. Recent examples of the importance of these findings in the onset or progression of neurodegenerative diseases are also discussed. This review should provide a profound insight into the role of redox homeostasis in microglial activity and help in the identification of new promising targets to control neuroinflammation through redox control of the brain.
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Cites
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
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Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
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Structure and function of the blood–brain barrier
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Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
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Cited by
Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease
Trist, B. G., Hare, D. J., & Double, K. L. (2019) · Aging Cell · doi:10.1111/acel.13031 · Cited by 778
Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach
Cuadrado, A., Manda, G., Hassan, A., Alcaraz, M. J., Barbas, C., Daiber, A., Ghezzi, P., León, R., López, M. G., Oliva, B., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014753 · Cited by 632
Self-citationThe impact of microglial activation on blood-brain barrier in brain diseases
da Fonseca, A. C. C., Matias, D., Garcia, C., Amaral, R., Geraldo, L. H., Freitas, C., & Lima, F. R. S. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00362 · Cited by 572
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Skvarc, D. R., Berk, M., Byrne, L. K., Dean, O. M., Dodd, S., Lewis, M., Marriott, A., Moore, E. M., Morris, G., Page, R. S., et al. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.11.011 · Cited by 312
Metadata
- Authors
- Rojo, A. I., McBean, G., Cindric, M., Egea, J., López, M. G., Rada, P., Zarkovic, N., & Cuadrado, A.
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2014-10-20
- Volume
- 21
- Issue
- 12
- Pages
- 1766-1801
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W2056633438
- Cited by
- 309
- References
- 64
- FWCI
- 10.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Rojo, A. I., McBean, G., Cindric, M., Egea, J., López, M. G., Rada, P., Zarkovic, N., & Cuadrado, A. (2014). Redox Control of Microglial Function: Molecular Mechanisms and Functional Significance. Antioxidants & Redox Signaling. https://doi.org/10.1089/ars.2013.5745
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