Microglial activation plays a pivotal role in neuroinflammation, which is increasingly recognized as a contributor to various neurological disorders. In a study examining graft-versus-host disease, it was found that inhibition of the colony-stimulating factor 1 receptor (CSF1R) led to increased neuroinflammation and behavioral deficits in mice, highlighting the dual role of microglia in both promoting and mitigating inflammation (ref: Adams doi.org/10.1182/blood.2023022040/). Another study demonstrated that MLKL deficiency alleviated neuroinflammation and motor deficits in a mouse model of Parkinson's disease, suggesting that targeting specific pathways in microglial activation could provide therapeutic benefits (ref: Geng doi.org/10.1186/s13024-023-00686-5/). Additionally, optogenetic stimulation of GABAergic neurons was shown to restore sleep and reprogram microglia in an Alzheimer's disease model, indicating that modulating neuronal activity can influence microglial behavior and neuroinflammatory responses (ref: Zhao doi.org/10.1186/s13024-023-00682-9/). The use of low-dose PLX5622 to partially deplete microglia prior to sepsis induction resulted in improved survival rates, further emphasizing the importance of microglial modulation in neuroinflammatory contexts (ref: Mein doi.org/10.1186/s12974-023-02975-8/). Moreover, spatially resolved transcriptomics revealed distinct patterns of glial cell activation in Alzheimer's disease, providing insights into the spatial dynamics of neuroinflammation (ref: Choi doi.org/10.1038/s12276-023-01123-9/).

Microglia are increasingly recognized for their role in neurodegenerative diseases, with studies revealing their involvement in the pathophysiology of conditions such as Alzheimer's and Parkinson's diseases. In a comprehensive analysis, it was shown that cell-type-specific polygenic risk scores for Alzheimer's disease are associated with distinct disease processes, with microglial risk factors correlating with neuroinflammation and cognitive decline (ref: Yang doi.org/10.1038/s41467-023-43132-2/). Furthermore, MLKL deficiency was found to alleviate neuroinflammation and motor deficits in a transgenic mouse model of Parkinson's disease, suggesting that targeting microglial pathways could be a viable therapeutic strategy (ref: Geng doi.org/10.1186/s13024-023-00686-5/). The neuroprotective effects of N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline against amyloid-β-induced neurotoxicity in Alzheimer's models further underscore the potential of targeting microglial responses to ameliorate disease symptoms (ref: Ali doi.org/10.3390/nu15234986/). Additionally, the role of microglial histone deacetylase 2 in traumatic brain injury was investigated, revealing that its absence did not significantly affect functional outcomes, suggesting that other pathways may compensate for its loss (ref: Zhang doi.org/10.1177/0271678X231197173/).

Microglia play a complex role in the tumor microenvironment, particularly in gliomas, where they can either promote or inhibit tumor progression. A study highlighted that glioma-derived ANXA1 suppresses the immune response to TLR3 ligands, thereby fostering an anti-inflammatory tumor microenvironment that hinders effective immune responses (ref: Zheng doi.org/10.1038/s41423-023-01110-0/). In contrast, research on dual cell membrane-coated doxorubicin-loaded nanoflakes demonstrated that microglial polarization can be manipulated to enhance anti-glioma effects, suggesting that targeted drug delivery systems could improve treatment efficacy (ref: Şen doi.org/10.1021/acsami.3c17097/). Furthermore, the use of polysialic acid-nanoparticles to inhibit macrophage-mediated inflammation presents a novel approach to managing age-related macular degeneration, indicating that microglial modulation could extend beyond the central nervous system (ref: Krishnan doi.org/10.3389/fimmu.2023.1237016/). The therapeutic potential of transcranial photobiomodulation in improving microglial function in diabetic models also points to the versatility of microglial targeting in various pathological contexts (ref: Liu doi.org/10.1038/s42003-023-05630-3/).

Microglia are integral to the immune response in the central nervous system, particularly following injuries such as spinal cord injury (SCI). A study revealed that thrombin-mediated expression of astrocytic chemokines drives sustained inflammatory activation after SCI, leading to excessive neuroinflammation (ref: He doi.org/10.1016/j.bbi.2023.11.035/). Additionally, the deficiency of indoleamine 2,3-dioxygenase 2 was associated with autism-like behaviors, highlighting the interplay between microglial function and neurodevelopmental outcomes (ref: Ishikawa doi.org/10.1111/febs.17019/). Lead exposure was shown to induce the release of pro-inflammatory chemokines in microglial cells, emphasizing the impact of environmental toxins on microglial activation and neuroinflammation (ref: Jiang doi.org/10.1016/j.toxlet.2023.12.001/). Furthermore, estrogens in the hippocampus were found to mitigate synaptic plasticity decline post-surgery by inhibiting microglial overactivation, suggesting a protective role for hormonal modulation in neuroinflammatory contexts (ref: Tan doi.org/10.1016/j.bbr.2023.114794/).

Microglial mechanisms are crucial in modulating pain and behavioral outcomes, particularly in neuroinflammatory conditions. Research demonstrated that the deficiency of indoleamine 2,3-dioxygenase 2 correlates with autism-like behavior through dopaminergic dysfunction, with altered microglial morphology contributing to these effects (ref: Ishikawa doi.org/10.1111/febs.17019/). Additionally, the administration of a mitochondrial fusion promoter during ischemia was found to provide greater neuroprotective effects compared to administration at reperfusion, indicating that timing in therapeutic interventions can significantly influence microglial responses and subsequent outcomes (ref: Chunchai doi.org/10.3233/JAD-230859/). The role of B-cell activating factor (BAFF) in regulating retinal ganglion cell damage through microglial activation and apoptosis pathways further underscores the importance of microglial function in neuroinflammatory pain models (ref: Lin doi.org/10.1016/j.intimp.2023.111287/). Moreover, the miR-99b-3p/Mmp13 axis was shown to regulate NLRP3 inflammasome-dependent microglial pyroptosis, highlighting potential therapeutic targets for alleviating neuropathic pain (ref: Gao doi.org/10.1016/j.intimp.2023.111331/).

Emerging therapeutic strategies targeting microglia are gaining traction in the treatment of various neurological disorders. The functional profiling of the G protein-coupled receptor C3aR1 revealed its potential as a druggable target, with implications for modulating microglial responses in inflammatory conditions (ref: Rodriguez doi.org/10.1016/j.jbc.2023.105549/). Lycopene was shown to alleviate chronic stress-induced microglial pyroptosis through the cathepsin B/NLRP3 signaling pathway, suggesting dietary interventions may offer therapeutic benefits in managing stress-related neuroinflammation (ref: Zhu doi.org/10.1021/acs.jafc.3c02749/). The clearance of neutrophils from the brain post-intracerebral hemorrhage by microglia, assisted by lactoferrin and CD91, highlights the importance of microglial efferocytosis in limiting secondary brain damage and inflammation (ref: Zhao doi.org/10.1161/STROKEAHA.123.045194/). Furthermore, the neuroprotective effects of N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline against amyloid-β-induced neurotoxicity in Alzheimer's models indicate that novel compounds derived from traditional medicine could provide new avenues for treatment (ref: Ali doi.org/10.3390/nu15234986/).

Microglial function is crucial in both development and aging, influencing cognitive outcomes and neurodegenerative processes. A study found that age-associated cortical similarity networks correlate with transcriptional signatures specific to cell types, including microglia, suggesting that changes in microglial function may contribute to cognitive decline with aging (ref: Niu doi.org/10.1093/cercor/). The clearance of neutrophils from the brain after intracerebral hemorrhage by microglia was shown to be beneficial, emphasizing the role of microglia in maintaining homeostasis in the aging brain (ref: Zhao doi.org/10.1161/STROKEAHA.123.045194/). Additionally, hippocampal estrogens were found to rescue synaptic plasticity decline post-surgery by inhibiting microglial overactivation, indicating that hormonal influences on microglial activity may play a role in cognitive health during aging (ref: Tan doi.org/10.1016/j.bbr.2023.114794/). Furthermore, the potential for neuronal conversion from glia to replenish lost neurons presents an exciting therapeutic strategy for neurodegenerative diseases characterized by significant neuronal loss (ref: Liang doi.org/10.4103/1673-5374.386400/).