Microglial activation plays a crucial role in neuroinflammation and is implicated in various neurological disorders. Recent studies have highlighted the importance of neuronal signals in regulating microglial phagocytosis, particularly in the developing retina, where neuronal signal-regulatory protein alpha (SIRPα) facilitates microglial activity by limiting interactions with CD47 (ref: Jiang doi.org/10.1016/j.immuni.2022.10.018/). Furthermore, the receptor for advanced glycation end products (RAGE) has been shown to influence glioma progression; its ablation suppresses pathways critical for tumor growth and enhances immune responses, indicating a potential therapeutic target in gliomas (ref: Zhang doi.org/10.1093/neuonc/). The role of microglia in neurodegenerative diseases is further underscored by findings that demonstrate how microglial TNFα orchestrates protein phosphorylation during sleep, suggesting a link between sleep regulation and neuroinflammation (ref: Pinto doi.org/10.15252/embj.2022111485/). In the context of neurodegenerative diseases like Parkinson's, microglial activation varies by brain region, impacting the inflammatory response and neuronal health (ref: Basurco doi.org/10.1002/glia.24295/). Additionally, SARS-CoV-2 infection has been shown to activate the NLRP3 inflammasome in human microglia, highlighting the virus's impact on neuroinflammation (ref: Albornoz doi.org/10.1038/s41380-022-01831-0/). Overall, these studies illustrate the multifaceted roles of microglia in both promoting and regulating neuroinflammation across various contexts.

Microglia are increasingly recognized for their dual roles in neurodegenerative diseases, acting both protectively and detrimentally. Research has shown that constitutive activation of the STING pathway leads to neuroinflammation and degeneration of dopaminergic neurons, a hallmark of diseases like Parkinson's (ref: Szego doi.org/10.7554/eLife.81943/). Additionally, Trem2 deficiency impairs microglial phagocytosis and recovery during viral-induced demyelination, suggesting that microglial function is critical for maintaining neuronal health in the face of viral challenges (ref: Hwang doi.org/10.1186/s12974-022-02629-1/). The characterization of microglial gene expression in models of multiple sclerosis has revealed distinct phenotypes at different disease stages, indicating that microglial activation is not uniform but rather context-dependent (ref: Vainchtein doi.org/10.1002/glia.24297/). Furthermore, severe Neuro-COVID has been linked to peripheral immune signatures and neurodegeneration, emphasizing the need for understanding the immune mechanisms underlying neurological manifestations of COVID-19 (ref: Etter doi.org/10.1038/s41467-022-34068-0/). Collectively, these findings highlight the complex interplay between microglial activation and neurodegenerative processes, suggesting that targeting microglial pathways may offer therapeutic avenues for these diseases.

Microglia are essential for proper neurodevelopment, influencing the formation and maintenance of neural circuits. Recent studies have demonstrated that microglia shape the embryonic development of respiratory networks, ensuring the correct wiring of brainstem circuits necessary for breathing (ref: Cabirol doi.org/10.7554/eLife.80352/). Additionally, the zebrafish microbiota has been shown to modulate microglial remodeling of forebrain neurons, linking microbial influences to social behavior through microglial activity during early development (ref: Bruckner doi.org/10.1371/journal.pbio.3001838/). These findings underscore the critical role of microglia not only in immune responses but also in shaping neural architecture and function during development. The implications of these studies extend to understanding how disruptions in microglial function could contribute to neurodevelopmental disorders, suggesting that interventions targeting microglial activity may be beneficial in promoting healthy brain development.

Microglial responses to injury are pivotal in mediating neuroinflammation and tissue repair. Studies have shown that oligodendrocyte precursor cells can ingest axons in the developing neocortex, highlighting the role of glial cells in synaptic refinement (ref: Buchanan doi.org/10.1073/pnas.2202580119/). Additionally, modified exosomal SIRPα variants have been found to enhance hematoma clearance and reduce secondary white matter injury following intracerebral hemorrhage, demonstrating the therapeutic potential of targeting microglial/macrophage modulation (ref: Gao doi.org/10.1186/s40824-022-00311-4/). Abrocitinib has also been shown to attenuate microglia-mediated neuroinflammation after traumatic brain injury by shifting microglial polarization towards an anti-inflammatory phenotype, which could improve outcomes for TBI patients (ref: Li doi.org/10.3390/cells11223588/). These studies collectively illustrate the dynamic role of microglia in responding to CNS injuries, emphasizing their potential as therapeutic targets in mitigating neuroinflammatory damage and promoting recovery.

Microglial interactions with other cell types are crucial for maintaining brain homeostasis and responding to injury. Research has shown that microglia-derived extracellular vesicles (EVs) can deliver microRNA-140-5p, which attenuates microglial activation and inflammatory responses following subarachnoid hemorrhage, indicating a protective role of microglial EVs in neuroinflammation (ref: Wang doi.org/10.1016/j.expneurol.2022.114265/). Furthermore, distinct characteristics of microglia from neurogenic and non-neurogenic regions of the human brain have been identified, revealing a greater proliferative capacity in neurogenic areas, which may influence their functional roles in various neurological conditions (ref: Smith doi.org/10.3389/fncel.2022.1047928/). Additionally, Gas6 has been shown to promote microglial efferocytosis and suppress inflammation through Axl/Rac1 signaling, further illustrating the complex signaling networks that govern microglial interactions with their environment (ref: Tang doi.org/10.1007/s12975-022-01099-0/). These findings highlight the importance of microglial interactions with other cell types in both health and disease, suggesting that targeting these interactions may provide new therapeutic strategies for neuroinflammatory and neurodegenerative disorders.