How to reprogram microglia toward beneficial functions

Marta Fumagalli, Marta Lombardi, Pierre Gressens, Claudia Verderio

Research output: Contribution to journalReview article

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2531-2549
Number of pages19
JournalGLIA
Volume66
Issue number12
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

Microglia
Brain
Inflammation
Immunomodulation
Brain Diseases
Metabolic Networks and Pathways
MicroRNAs
Energy Metabolism
Regeneration
Ischemia
Mothers
Pharmacology
Pathology
Cytokines
Phenotype
Lipids
Wounds and Injuries
Therapeutics
Infection

Keywords

  • beneficial phenotype
  • metabolism
  • microglia
  • miRNA
  • re-program

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

How to reprogram microglia toward beneficial functions. / Fumagalli, Marta; Lombardi, Marta; Gressens, Pierre; Verderio, Claudia.

In: GLIA, Vol. 66, No. 12, 01.12.2018, p. 2531-2549.

Research output: Contribution to journalReview article

Fumagalli, Marta ; Lombardi, Marta ; Gressens, Pierre ; Verderio, Claudia. / How to reprogram microglia toward beneficial functions. In: GLIA. 2018 ; Vol. 66, No. 12. pp. 2531-2549.
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