Recent Advances in Microglial Activation

Microglia are the main myeloid cells in the central nervous system (CNS), being considered as the resident macrophages of the nervous parenchyma. In physiological non-pathological conditions, microglial cells are involved in numerous processes, such as cellular debris clearance, formation and refinement of neural circuits through synaptic pruning, regulation of adult neurogenesis, blood–brain barrier maintenance, myelination and remyelination, and surveillance of CNS homeostasis. Regarding this last function, microglia act as sentinels by scanning the surrounding media with their motile processes in search of signs of tissue damage or pathogenic microorganisms. To sense molecular cues produced in those events that compromise CNS homeostasis, microglia are decorated with a variety of receptors, which are collectively called pattern recognition receptors (PRRs). PRRs allow them to detect both exogenous pathogen associated molecular patterns (PAMPs) and endogenous damage associated molecular patterns (DAMPs) or alarmins. Binding of PAMPs or DAMPs to microglial PRRs triggers the activation of signaling pathways that result in the nuclear translocation of the nuclear factor kappa beta or inflammasome formation, and the activation of microglia.

Activated microglia undergo significant changes, prominently the secretion of inflammatory mediators (e.g., cytokines, chemokines, and growth factors), increased motility, and enhanced phagocytic capacity. Moreover, activation allows microglia to arrange the immune response within the CNS. While activated microglia work towards pathogen clearance and the restoration of homeostasis, overactive or dysregulated microglia may lead to neurotoxicity and neurodegeneration. Therefore, the modulation of microglial activation is particularly relevant—especially in those cases where they undergo a strong acute activation or a chronic activation. Likewise, microglial priming (a pseudo-resting state characterized by a hyper-sensitivity and exacerbated response to inflammatory stimuli) and the factors leading to this state are of the highest interest, since primed microglia may mediate neurodegenerative processes. The purpose of this Special Issue is to draw in original research articles as well as reviews that will increase our current knowledge on microglial activation, particularly regarding the molecules involved as well as pathological states that induce such activation. Novel methodologies to evaluate the activation process will be welcomed.

Prof. Jesús Mateos Grondona
Prof. María Dolores López Ávalos
Guest Editors

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• microglia
• neuroinflammation
• priming
• neurodegeneration
• PRRs
• DAMPs
• PAMPs