Microglial activation plays a pivotal role in neuroinflammation and neurodegeneration, as evidenced by various studies. For instance, Khazaei et al. demonstrated that specific histone mutations (H3.3G34R/V) lead to progressive neurodegeneration and microcephaly in mice, correlating with increased disease-associated microglia and neuronal depletion (ref: Khazaei doi.org/10.1016/j.cell.2023.02.023/). Similarly, Mi et al. found that impaired fatty acid degradation in astrocytic mitochondria triggers neuroinflammation, highlighting the metabolic dependencies of astrocytes in maintaining neuronal health (ref: Mi doi.org/10.1038/s42255-023-00756-4/). In a different context, Nikolopoulos et al. explored the role of microglial activation in systemic lupus erythematosus, revealing that inflammatory mediators disrupt hippocampal neurogenesis, which is critical for cognitive function (ref: Nikolopoulos doi.org/10.1136/ard-2022-223506/). Furthermore, Zhou et al. identified the neuronal pentraxin Nptx2 as a regulator of complement activity, which restrains microglia-mediated synapse loss, suggesting that complement overactivation exacerbates neurodegeneration in conditions like Alzheimer's disease (ref: Zhou doi.org/10.1126/scitranslmed.adf0141/). These findings collectively underscore the multifaceted roles of microglia in neuroinflammatory processes and their implications for neurodegenerative diseases.

Microglia are increasingly recognized for their dual roles in neurodegenerative diseases, acting both protectively and detrimentally. For example, Winfree et al. highlighted the region-specific expression of TREM2 in relation to Alzheimer's disease pathology, showing that cortical TREM2 levels correlate positively with cognitive decline, while caudate TREM2 levels relate to microglial activation (ref: Winfree doi.org/10.1007/s00401-023-02564-2/). In contrast, Malpetti et al. demonstrated that increased microglial activation in the frontal cortex predicts cognitive decline in frontotemporal dementia, emphasizing the predictive value of neuroinflammation in cognitive deterioration (ref: Malpetti doi.org/10.1093/brain/). Additionally, Zahaf et al. reported sex-dependent differences in microglial androgen receptor expression, suggesting that androgens may modulate neuroinflammatory responses differently in males and females (ref: Zahaf doi.org/10.1038/s41467-023-36846-w/). These studies illustrate the complex interplay between microglial activity and neurodegenerative processes, indicating that targeting microglial functions could offer therapeutic avenues for managing these diseases.

The interactions between microglia and other cell types are crucial for understanding their role in brain pathology. Yang et al. investigated how polio virotherapy targets the myeloid infiltrate in malignant gliomas, revealing that microglial activation is essential for the therapeutic response (ref: Yang doi.org/10.1093/neuonc/). Furthermore, Huang et al. explored the influence of the gut microbiome on microglial transformation, demonstrating that gut microbiota disturbances can modulate microglial activity and potentially contribute to brain diseases (ref: Huang doi.org/10.1038/s41380-023-02017-y/). In the context of neuroinflammation, Cui et al. found that vitamin D signaling in microglia/macrophages is vital for restraining neuroinflammation and brain injury following ischemic stroke, suggesting that immune modulation could be a therapeutic target (ref: Cui doi.org/10.1186/s12974-023-02705-0/). These findings highlight the significance of microglial interactions with other cell types in both disease progression and recovery.

Recent studies have elucidated various genetic and molecular mechanisms that govern microglial function in health and disease. Anderson et al. utilized single nucleus multiomics to identify candidate regulators of Alzheimer's disease-specific transcriptional changes, revealing critical insights into the molecular underpinnings of microglial responses (ref: Anderson doi.org/10.1016/j.xgen.2023.100263/). Additionally, the work by Weinschutz Mendes et al. on autism spectrum disorder genes highlighted the convergence of neuroimmune pathways, suggesting that genetic factors influencing microglial function may also affect neurodevelopmental outcomes (ref: Weinschutz Mendes doi.org/10.1016/j.celrep.2023.112243/). Moreover, de Dios et al. investigated inflammasome activation in the context of high cholesterol, demonstrating that persistent inflammation can lead to a protective microglial phenotype while promoting neuronal pyroptosis (ref: de Dios doi.org/10.1186/s40035-023-00343-3/). These studies collectively emphasize the intricate genetic and molecular landscape that shapes microglial behavior and their implications for neurodegenerative and neurodevelopmental disorders.

Therapeutic strategies targeting microglial function are gaining traction in the context of neurodegenerative diseases. For instance, Wheeler et al. developed a novel droplet-based genetic screening platform to explore astrocyte-microglia interactions, which could unveil new therapeutic targets for modulating neuroinflammation (ref: Wheeler doi.org/10.1126/science.abq4822/). In a related study, Soula et al. examined the effects of 40-Hz light stimulation on amyloid-beta levels in Alzheimer's disease models, finding that this noninvasive approach did not engage native gamma oscillations, thus questioning its efficacy as a therapeutic intervention (ref: Soula doi.org/10.1038/s41593-023-01270-2/). Additionally, Chu et al. identified the SWELL1 channel in spinal microglia as a contributor to neuropathic pain, suggesting that targeting ATP release mechanisms may provide relief in pain management (ref: Chu doi.org/10.1126/sciadv.ade9931/). These studies highlight the potential of innovative therapeutic approaches aimed at modulating microglial activity to improve outcomes in neurodegenerative diseases.

Microglia play a critical role in brain injury and recovery processes. Khazaei et al. demonstrated that specific histone mutations lead to neurodegeneration and abnormal microglial accumulation, indicating that microglial responses are integral to the pathophysiology of brain injuries (ref: Khazaei doi.org/10.1016/j.cell.2023.02.023/). In the context of ischemic stroke, Cui et al. found that vitamin D signaling in microglia is essential for mitigating neuroinflammation and promoting recovery, suggesting that enhancing this pathway could improve clinical outcomes (ref: Cui doi.org/10.1186/s12974-023-02705-0/). Furthermore, the study by Mi et al. on astrocytic mitochondrial function revealed that disruptions in fatty acid degradation can trigger neuroinflammation, emphasizing the interconnectedness of glial cells in response to brain injury (ref: Mi doi.org/10.1038/s42255-023-00756-4/). These findings collectively underscore the importance of microglial function in the context of brain injury and recovery, highlighting potential therapeutic avenues for enhancing neuroprotection and repair.

Microglia are increasingly recognized for their role in cognitive function, particularly in neurodegenerative contexts. Malpetti et al. found that increased microglial activation in the frontal cortex correlates with faster cognitive decline in frontotemporal dementia, suggesting that neuroinflammation is a significant predictor of cognitive deterioration (ref: Malpetti doi.org/10.1093/brain/). Additionally, Winfree et al. reported that TREM2 expression in the caudate is associated with microglial activation and cognitive performance in Alzheimer's disease, indicating that microglial responses may influence cognitive outcomes (ref: Winfree doi.org/10.1007/s00401-023-02564-2/). Zahaf et al. also highlighted the impact of sex differences on microglial function and myelination, suggesting that androgens may modulate cognitive functions through their effects on microglial activity (ref: Zahaf doi.org/10.1038/s41467-023-36846-w/). These studies collectively emphasize the critical role of microglia in cognitive processes and their potential as therapeutic targets for cognitive decline in neurodegenerative diseases.