How to reprogram microglia toward beneficial functions. Issue 12 (8th September 2018)

• Record Type: Journal Article
• Authors: Fumagalli, Marta; Lombardi, Marta; Gressens, Pierre; Verderio, Claudia
• Is Part Of: Glia. Volume 66:Issue 12(2018)
• Page Start: 2531
• Page End: 2549
• Publication Date: 2018-09-08
• Subjects: beneficial phenotype -- metabolism -- microglia -- miRNA -- re‐program; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23484
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Microglia, brain cells of nonneural origin, orchestrate the inflammatory response to diverse insults, including hypoxia/ischemia or maternal/fetal infection in the perinatal brain. Experimental studies have demonstrated the capacity of microglia to recognize pathogens or damaged cells activating a cytotoxic response that can exacerbate brain damage. However, microglia display an enormous plasticity in their responses to injury and may also promote resolution stages of inflammation and tissue regeneration. Despite the critical role of microglia in brain pathologies, the cellular mechanisms that govern the diverse phenotypes of microglia are just beginning to be defined. Here we review emerging strategies to drive microglia toward beneficial functions, selectively reporting the studies which provide insights into molecular mechanisms underlying the phenotypic switch. A variety of approaches have been proposed which rely on microglia treatment with pharmacological agents, cytokines, lipid messengers, or microRNAs, as well on nutritional approaches or therapies with immunomodulatory cells. Analysis of the molecular mechanisms relevant for microglia reprogramming toward pro‐regenerative functions points to a central role of energy metabolism in shaping microglial functions. Manipulation of metabolic pathways may thus provide new therapeutic opportunities to prevent the deleterious effects of inflammatory microglia and to control excessive inflammation in brain disorders. Main Points: Key inflammatory pathways are fueled by glucose flux through glycolysis. Anti‐inflammatory miRNAs target metabolic genes. Stem cells which redirect microglia towards protective function influence metabolism.