2021
DOI: 10.3389/fncel.2021.736310
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Microglial Phenotypic Transition: Signaling Pathways and Influencing Modulators Involved in Regulation in Central Nervous System Diseases

Abstract: Microglia are macrophages that reside in the central nervous system (CNS) and belong to the innate immune system. Moreover, they are crucially involved in CNS development, maturation, and aging; further, they are closely associated with neurons. In normal conditions, microglia remain in a static state. Upon trauma or lesion occurrence, microglia can be activated and subsequently polarized into the pro-inflammatory or anti-inflammatory phenotype. The phenotypic transition is regulated by numerous modulators. Th… Show more

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Cited by 46 publications
(29 citation statements)
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References 173 publications
(234 reference statements)
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“…Furthermore, while microglial activation has been previously viewed to be polarized that view is no longer held. In fact, microglia transcriptomics has established how they can express both proinflammatory and anti-inflammatory molecules at the same time ( Chen and Trapp, 2016 ; De Biase et al, 2017 ; Li et al, 2021 ), which is a topic for further investigation given the context of current findings.…”
Section: Discussionmentioning
confidence: 81%
“…Furthermore, while microglial activation has been previously viewed to be polarized that view is no longer held. In fact, microglia transcriptomics has established how they can express both proinflammatory and anti-inflammatory molecules at the same time ( Chen and Trapp, 2016 ; De Biase et al, 2017 ; Li et al, 2021 ), which is a topic for further investigation given the context of current findings.…”
Section: Discussionmentioning
confidence: 81%
“…Pro-inflammatory, often referred to as M1-like, microglia are induced by tissue injury and phlogistic soluble factors. In particular, the presence of bacterial components (e.g., LPS) and cellular debris, as well as of IL-1β, IL-8, IFNγ and TNF in the surrounding milieu, induces the activation inflammasome complexes, such as NOD-like receptor family pyrin 1 and 3 (NRLP1 and 3) and, consequently, the release of neuroinflammatory factors, such as the pro-inflammatory cytokines (e.g., IL-1α/β, IL-6, IL-23 and TNF), chemokines (e.g., CCL2, CXCL9, CXCL10 and CCL20), co-stimulatory proteins (e.g., CD40 and MHC-II) and the activation of enzymes involved in the induction of oxidative stress (e.g., NADPH oxidase and the inducible nitric oxide synthase (iNOS)), which result in excitotoxicity, neurotoxicity, demyelination and, ultimately, neuronal dysfunction and death [ 14 , 26 , 27 ]. Alongside the induction of the aforementioned factors, M1-like polarization is often accompanied by an upregulation of CD11b, CD16/32, CD68 and CD86, with the concomitant activation of typical transcription factors, also previously described for peripheral macrophages, such as NF-kB, STAT1 and STAT3 [ 28 ].…”
Section: Microgliamentioning
confidence: 99%
“…The activation of microglia and astrocytes as a reaction to the ongoing deposition of Aβ and NFTs triggers the production of several proinflammatory signal molecules including cytokines, chemokines, complement molecules, growth factors, and cell adhesion molecules. Previous studies suggest that microglia transition from a largely anti-inflammatory/pro-phagocytic (M2) to a pro-inflammatory/neurotoxic (M1) activation state during AD progression [ 140 ]. Profiling of microglia transcriptome in mouse models of Aβ accumulation and AD patients has revealed a robust transcriptional activation signature which has been referred to as disease-associated microglia (DAM), which is quite distinct from that of homeostatic microglia [ 141 ].…”
Section: Inflammation and Admentioning
confidence: 99%