Interplay between autophagy and the NLRP3 inflammasome in microglia

Microglia are a type of glial cells that protect the nervous system from pathogens and toxic molecules, contributing to the maintenance of the brain’s homeostasis. Microglia are part of our innate immune system. Pathogen infection and misfolded protein aggregates can induce inflammasome activation in microglia. Inflammasomes are multi-protein complexes that assemble to promote the release of pro-inflammatory cytokines, such as IL-1β. Evidence from the literature suggests that inflammasome overactivation contributes to neuroinflammation, which is an established hallmark of neurodegenerative diseases. Neuroinflammation is an inflammatory response, triggered by reactive microglia, aimed at restoring homeostasis in damaged nervous tissue. However, dysregulation of inflammasome signaling can result in a chronic neuroinflammatory state, with detrimental consequences for the neuronal tissue. Since inflammasomes are mainly degraded through autophagy, which is known to be downregulated during aging and in neurodegenerative disease, an impairment of this process in microglia may result in a state of chronic neuroinflammation. Therefore, the project aims to investigate the interplay between autophagy and the NLRP3 inflammasome in microglia by monitoring the autophagic flux in the BV2 murine microglial cell line under basal and inflammatory conditions and assessing how impaired autophagy affects the degradation of the NLRP3 inflammasome and cytokines release.