Life and death of microglia: Mechanisms governing microglial states and fates.

Recent advances in genetic analysis and intensive research have revealed that microglial cells respond to external stimuli in various ways and adopt diverse states. Herein, we summarize the current knowledge on the possible microglial states during development, homeostasis, and perturbation. These states are characterized either by irreversible cellular changes, such as cell death and cellular senescence, or reversible alterations, triggered by temporary changes in the microenvironment. Subsequently, we discuss the modalities of the transcriptional and functional recovery of microglia from a molecular perspective. An understanding of (ir)reversible changes in their cellular fates or transcriptional states could provide novel options for the treatment of age-related and neurodegenerative disorders.