Microglia play a crucial role in neuroinflammation and neurodegenerative diseases, as highlighted by several studies. Rao et al. demonstrated that microglial depletion in a chimeric Alzheimer's disease model significantly reduced human neuronal APOE4-related pathologies, suggesting that microglia interact closely with neuronal APOE4 in the pathogenesis of Alzheimer's disease (ref: Rao doi.org/10.1016/j.stem.2024.10.005/). Gruber et al. explored the role of Bruton's tyrosine kinase (BTK) in regulating microglial function and neuroinflammation in multiple sclerosis models, proposing that BTK inhibition could be a therapeutic strategy to mitigate neuroinflammation and disability (ref: Gruber doi.org/10.1038/s41467-024-54430-8/). Furthermore, Clarke et al. found that VCP mutant microglia displayed unique immune and lysosomal phenotypes, indicating that microglial responses can vary significantly depending on genetic factors (ref: Clarke doi.org/10.1186/s13024-024-00773-1/). These findings collectively underscore the importance of microglial activation states in various neurodegenerative contexts and their potential as therapeutic targets. In addition to these findings, Sobue et al. investigated the effects of cannabinoid receptor type II stimulation on microglial activation in Alzheimer's disease mice, revealing that this stimulation improved cognitive impairment and reduced neuroinflammation by modulating astrocyte activation (ref: Sobue doi.org/10.1038/s41419-024-07249-6/). Kong et al. further contributed to this theme by showing that STING orchestrates microglial polarization through autophagy regulation following ischemic injury, highlighting the dual role of autophagy in microglial function (ref: Kong doi.org/10.1038/s41419-024-07208-1/). Zhang et al. also provided insights into the role of the microglial receptor TREM2 in synaptic pruning, which is crucial for fear memory formation, indicating that microglia are integral to synaptic plasticity and cognitive functions (ref: Zhang doi.org/10.3389/fimmu.2024.1412699/). Overall, these studies illustrate the multifaceted roles of microglia in neuroinflammation and their potential as therapeutic targets in neurodegenerative diseases.

The role of microglia in neurodegenerative diseases is increasingly recognized, with several studies elucidating their involvement in conditions such as Alzheimer's disease and multiple sclerosis. Ma et al. conducted a spatial transcriptomic analysis revealing that immunoglobulin-associated senescence is a hallmark of aging, with microglial activation being a significant feature in aged tissues (ref: Ma doi.org/10.1016/j.cell.2024.10.019/). Alsema et al. focused on multiple sclerosis, generating spatial gene expression maps that identified distinct gene signatures associated with white matter lesion progression, emphasizing the role of microglia in the inflammatory processes underlying this disease (ref: Alsema doi.org/10.1038/s41593-024-01765-6/). Ishii et al. further investigated the contribution of oligodendrocytes to amyloid deposition in Alzheimer's disease, suggesting that microglial interactions with oligodendrocytes may influence amyloid pathology (ref: Ishii doi.org/10.1186/s13024-024-00759-z/). In addition, Arber et al. highlighted the role of microglia in familial British dementia, showing that microglial expression of ITM2B/BRI2 is significantly higher than in neurons, indicating a unique microglial contribution to amyloid pathology (ref: Arber doi.org/10.1007/s00401-024-02820-z/). Pan et al. also demonstrated that microglia facilitate the clearance of amyloid-beta in Alzheimer's disease, underscoring their critical role in maintaining brain homeostasis (ref: Pan doi.org/10.1002/advs.202412184/). Collectively, these studies illustrate the complex interplay between microglia and neurodegenerative processes, highlighting their potential as therapeutic targets for modulating disease progression.

Aging significantly impacts microglial function and contributes to neurodegenerative diseases, as evidenced by recent research. Ma et al. provided a comprehensive spatial transcriptomic profile of aging tissues, revealing that the accumulation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding senescence-sensitive spots, indicating that microglial activation is a hallmark of aging (ref: Ma doi.org/10.1016/j.cell.2024.10.019/). Maurya et al. explored the regulation of disease-associated microglia in the optic nerve, demonstrating that lipoxin B can modulate microglial phenotypes in response to retinal stress, which is crucial for understanding age-related neurodegeneration (ref: Maurya doi.org/10.1186/s13024-024-00775-z/). Moreover, Kong et al. discussed the role of STING in orchestrating microglial polarization after ischemic injury, suggesting that autophagy may play a dual role in microglial function during aging (ref: Kong doi.org/10.1038/s41419-024-07208-1/). Marciante et al. reported that microglia regulate motor neuron plasticity through fractalkine and adenosine signaling, highlighting the importance of microglial interactions in maintaining neural plasticity during aging (ref: Marciante doi.org/10.1038/s41467-024-54619-x/). These findings collectively underscore the critical role of microglia in aging and their potential as therapeutic targets for age-related neurodegenerative diseases.

Microglia are pivotal in the response to brain injury and subsequent repair processes. Su et al. investigated the use of chitosan-modified hydrogel microspheres encapsulating zinc-doped bioactive glasses for spinal cord injury repair, demonstrating that these microspheres effectively inhibited microglial activation and promoted angiogenesis, thereby enhancing recovery (ref: Su doi.org/10.1002/adhm.202402129/). Kong et al. also contributed to this theme by showing that STING orchestrates microglial polarization in response to ischemic injury, indicating that microglial activation states can influence recovery outcomes (ref: Kong doi.org/10.1038/s41419-024-07208-1/). Furthermore, Huré et al. employed a pharmacogenomic approach to identify compounds that promote oligodendrogenesis in brain repair, highlighting the importance of microglial interactions in facilitating myelin repair processes (ref: Huré doi.org/10.1038/s41467-024-54003-9/). Xu et al. introduced immunomodulatory microspheres that enhance neurovascular crosstalk and promote neural repair following ischemic stroke, emphasizing the therapeutic potential of modulating microglial activity in brain injury contexts (ref: Xu doi.org/10.1016/j.bioactmat.2024.10.031/). These studies collectively illustrate the critical roles of microglia in mediating responses to brain injury and facilitating repair mechanisms.

Microglia are integral to the immune response in the central nervous system, with recent studies elucidating their roles in various pathological contexts. Maurya et al. highlighted the regulation of disease-associated microglia in the optic nerve by lipoxin B, demonstrating that microglia undergo dynamic changes in response to retinal stress, which is crucial for understanding neurodegenerative processes (ref: Maurya doi.org/10.1186/s13024-024-00775-z/). Clarke et al. examined the immune and lysosomal phenotypes of VCP mutant microglia, revealing differential activation of inflammatory pathways compared to healthy microglia, indicating that genetic factors can influence microglial immune responses (ref: Clarke doi.org/10.1186/s13024-024-00773-1/). Additionally, Buonfiglioli et al. developed a microglia-containing cerebral organoid model to study early life immune challenges, providing insights into how maternal immune activation can affect neurodevelopment (ref: Buonfiglioli doi.org/10.1016/j.bbi.2024.11.008/). Huré et al. also contributed to this theme by identifying pharmacogenomic compounds that enhance oligodendrogenesis, suggesting that microglial modulation can influence immune responses in the context of brain repair (ref: Huré doi.org/10.1038/s41467-024-54003-9/). These findings collectively underscore the complex interplay between microglia and the immune response in the central nervous system.

Microglia are increasingly recognized for their role in synaptic function and plasticity, with several studies highlighting their involvement in cognitive processes. Clarke et al. demonstrated that VCP mutant microglia exhibit altered immune and lysosomal phenotypes, which may impact synaptic health and function (ref: Clarke doi.org/10.1186/s13024-024-00773-1/). Zhang et al. specifically investigated the role of the microglial receptor TREM2 in synaptic pruning, showing that TREM2 is crucial for fear memory formation through its effects on synaptic loss and neuron activity (ref: Zhang doi.org/10.3389/fimmu.2024.1412699/). Moreover, the study by Sobue et al. on cannabinoid receptor type II stimulation revealed that modulating microglial activation can improve cognitive impairment in Alzheimer's disease models, suggesting that microglia play a significant role in maintaining synaptic integrity (ref: Sobue doi.org/10.1038/s41419-024-07249-6/). Additionally, Nagarajan et al. found that microglial involvement in the trigeminal system is crucial for modulating headache-like symptoms, indicating that microglia may influence synaptic responses in pain pathways (ref: Nagarajan doi.org/10.1186/s10194-024-01897-x/). These studies collectively highlight the essential roles of microglia in synaptic function and their potential implications for cognitive health.

Microglial metabolism and homeostasis are critical for maintaining central nervous system health, with recent studies shedding light on the underlying mechanisms. Quijano et al. investigated the modulation of mitochondrial dynamics by the angiotensin system in microglia, revealing that activation of microglial cells leads to increased mitochondrial fission and superoxide production, which can be inhibited by Angiotensin 1-7 treatment (ref: Quijano doi.org/10.14336/AD.2024.0981/). This suggests that metabolic pathways play a significant role in regulating microglial function and response to injury. Kong et al. also contributed to this theme by demonstrating that STING orchestrates microglial polarization through autophagy regulation, indicating that metabolic processes are intertwined with microglial activation states following ischemic injury (ref: Kong doi.org/10.1038/s41419-024-07208-1/). Xu et al. further emphasized the importance of immune-neurovascular crosstalk in promoting neural repair, highlighting how microglial metabolism can influence recovery outcomes after injury (ref: Xu doi.org/10.1016/j.bioactmat.2024.10.031/). These findings collectively underscore the critical roles of microglial metabolism and homeostasis in maintaining central nervous system health and responding to injury.

Genetic factors significantly influence microglial function and their responses to environmental stimuli, as evidenced by recent research. Li et al. explored the impact of polygenic risk for alcohol use disorder on cellular responses in human microglial models, revealing that genetic susceptibility can modulate microglial activation and inflammatory responses to ethanol exposure (ref: Li doi.org/10.1126/sciadv.ado5820/). This study highlights the importance of understanding genetic predispositions in the context of neuroimmune interactions. Huré et al. also contributed to this theme by identifying pharmacogenomic compounds that promote oligodendrogenesis, suggesting that genetic factors can influence microglial activity and their role in brain repair (ref: Huré doi.org/10.1038/s41467-024-54003-9/). Additionally, Zhang et al. demonstrated that TREM2, a gene associated with Alzheimer's disease, plays a crucial role in synaptic pruning and memory formation, indicating that genetic variations can affect microglial functions related to cognitive processes (ref: Zhang doi.org/10.3389/fimmu.2024.1412699/). These findings collectively underscore the complex interplay between genetic factors and microglial function in health and disease.