Microglial activation plays a pivotal role in neuroinflammation, particularly in the context of various neurological disorders. Recent studies have highlighted the pathological features associated with COVID-19, revealing that severe neurological symptoms correlate with monocytic encephalitis, characterized by significant infiltration of inflammatory cells in the brains of critically ill patients (ref: Zhang doi.org/10.1038/s41392-022-01291-6/). In Alzheimer's disease (AD), the activation of microglia through TREM2 has emerged as a potential therapeutic target, with a TREM2-activating antibody demonstrating enhanced microglial metabolism and improved brain biodistribution (ref: van Lengerich doi.org/10.1038/s41593-022-01240-0/). Furthermore, the role of microglia in mediating brain injury following transient insults, such as radiation-induced brain injury, has been elucidated, showing that microglia can drive CD8 T cell recruitment, exacerbating damage (ref: Shi doi.org/10.1016/j.neuron.2022.12.009/). Additionally, the use of CSF1R inhibitors has been shown to induce a resilient microglial phenotype, suggesting a nuanced role of microglia in tauopathies (ref: Johnson doi.org/10.1038/s41467-022-35753-w/). The temporal dynamics of microglial synapse pruning in neuropathic pain further illustrate the complexity of microglial functions, with distinct patterns of synapse removal observed (ref: Yousefpour doi.org/10.1016/j.celrep.2023.112010/). Moreover, neuroinflammation induced by non-replicating SARS-CoV-2 variants highlights the potential for long-term cognitive impairments associated with COVID-19 (ref: Erickson doi.org/10.1016/j.bbi.2023.01.010/).

Microglia are increasingly recognized for their dual roles in neurodegenerative diseases, particularly in Alzheimer's disease (AD). The activation of microglia through the TREM2 pathway has been linked to both protective and detrimental effects in AD progression, with studies indicating that sTREM2 levels correlate with amyloid-related pathology and metabolic changes in the brain (ref: Biel doi.org/10.15252/emmm.202216987/). Additionally, the dysregulation of transposable elements in response to tau pathology has been implicated in AD, suggesting a complex interplay between microglial activation and disease mechanisms (ref: Evering doi.org/10.1016/j.tins.2022.12.003/). The use of CSF1R inhibitors has shown promise in promoting a resilient microglial phenotype in tauopathy models, indicating potential therapeutic avenues (ref: Johnson doi.org/10.1038/s41467-022-35753-w/). Furthermore, the role of FUT8-catalyzed fucosylation in microglial activation in response to amyloid-beta oligomers underscores the importance of metabolic pathways in modulating microglial responses (ref: Jin doi.org/10.1002/glia.24345/). The therapeutic efficacy of PPARα activation in juvenile neuronal ceroid lipofuscinosis models further highlights the potential for targeting microglial functions in neurodegenerative conditions (ref: Jana doi.org/10.1523/JNEUROSCI.2447-21.2023/).

Microglia play a critical role in the tumor microenvironment, particularly in glioblastoma (GBM), where their metabolic state significantly influences therapeutic outcomes. Recent findings indicate that targeting microglial metabolic rewiring can enhance the efficacy of immune-checkpoint blockade therapies in GBM, revealing the potential for synergistic treatment strategies (ref: Ye doi.org/10.1158/2159-8290.CD-22-0455/). Furthermore, the development of GBMdeconvoluteR has facilitated the characterization of immune and neoplastic cell populations within GBM tumors, providing insights into the cellular landscape and its implications for clinical outcomes (ref: Ajaib doi.org/10.1093/neuonc/). The interaction between glioma-associated microglia/macrophages and anti-PD-1 therapy has also been explored, demonstrating that M1-like microglia enhance therapeutic responses while M2-like microglia contribute to resistance (ref: Wang doi.org/10.1007/s00262-022-03358-3/). These studies underscore the complexity of microglial interactions within the tumor microenvironment and their impact on treatment efficacy.

The metabolic state of microglia is crucial for their functionality and response to neuroinflammatory conditions. Recent research has shown that microglia under oxidative stress exhibit altered metabolic pathways, which can be targeted to enhance therapeutic responses in glioblastoma (ref: Ye doi.org/10.1158/2159-8290.CD-22-0455/). In the context of traumatic brain injury (TBI), inhibiting autophagy in microglia has been linked to exacerbated inflammatory responses and worsened outcomes, highlighting the importance of metabolic regulation in microglial activation (ref: Hegdekar doi.org/10.1080/15548627.2023.2167689/). Additionally, the temporal dynamics of microglial synapse pruning in neuropathic pain reveal that microglia selectively remove inhibitory synapses before excitatory ones, indicating a sophisticated regulatory mechanism (ref: Yousefpour doi.org/10.1016/j.celrep.2023.112010/). Furthermore, studies have demonstrated that microglia rely on SYK signaling to mount neuroprotective responses, emphasizing the critical role of metabolic pathways in modulating their functions in neurodegenerative diseases (ref: Ennerfelt doi.org/10.1002/ctm2.1178/).

Microglia are integral to the immune response in the central nervous system, with their activation influencing various pathological conditions. The TREM2 pathway has been identified as a key regulator of microglial metabolism, with a TREM2-activating antibody showing promise in enhancing microglial functions in Alzheimer's disease models (ref: van Lengerich doi.org/10.1038/s41593-022-01240-0/). Additionally, the role of T follicular helper cells in neuromyelitis optica spectrum disorders has been explored, revealing their contribution to disease pathophysiology and the activation of microglia (ref: Yick doi.org/10.1172/jci.insight.161003/). The FGF/FGFR signaling pathway has also been implicated in microglial activation during Lyme neuroborreliosis, suggesting a potential intersection with other neurological conditions (ref: Parthasarathy doi.org/10.1186/s12974-022-02681-x/). Furthermore, the inhibitory effects of baricitinib on microglia in rheumatoid arthritis models highlight the therapeutic potential of targeting microglial activation in systemic inflammatory conditions (ref: Matsushita doi.org/10.1093/rheumatology/).

The interaction of microglia with other cell types is crucial for maintaining homeostasis and responding to injury in the central nervous system. Recent studies have shown that inhibiting autophagy in microglia and macrophages exacerbates inflammatory responses and worsens outcomes following brain injury, underscoring the importance of microglial interactions with neuronal cells (ref: Hegdekar doi.org/10.1080/15548627.2023.2167689/). The characterization of microglial behavior in both healthy and pathological conditions has been enhanced through image analysis tools, allowing for a better understanding of their morphological and functional adaptations (ref: Martinez doi.org/10.1098/rsob.220200/). Additionally, the inflammatory foreign-body response to neuroimplants has been shown to differ between young and adult rats, with implications for microglial behavior and tissue recovery following implantation (ref: Sharon doi.org/10.1016/j.actbio.2023.01.002/). The role of Alpinetin in inhibiting neuroinflammation and neuronal apoptosis through microglial activation further highlights the significance of microglial interactions in neuroprotection (ref: Xiao doi.org/10.1111/cns.14085/).

Therapeutic strategies targeting microglia have gained traction in recent research, particularly in the context of neurodegenerative diseases and cancer. The development of a TREM2-activating antibody that enhances microglial metabolism presents a promising avenue for Alzheimer's disease treatment, demonstrating improved brain biodistribution and signaling (ref: van Lengerich doi.org/10.1038/s41593-022-01240-0/). Additionally, targeting microglial metabolic rewiring has shown potential in synergizing with immune-checkpoint blockade therapies for glioblastoma, indicating the importance of metabolic pathways in therapeutic efficacy (ref: Ye doi.org/10.1158/2159-8290.CD-22-0455/). The use of CSF1R inhibitors has also been explored, revealing their ability to induce a resilient microglial phenotype and reduce pathogenic tau in tauopathy models (ref: Johnson doi.org/10.1038/s41467-022-35753-w/). Furthermore, the role of FUT8-catalyzed core fucosylation in microglial activation in response to amyloid-beta oligomers highlights the potential for targeting specific metabolic pathways to modulate microglial functions (ref: Jin doi.org/10.1002/glia.24345/).