Microglial function plays a critical role in the pathophysiology of neurodegenerative diseases, particularly Alzheimer's disease (AD). Recent studies have highlighted the influence of reactive astrocytes on microglial behavior, particularly in the context of amyloid plaque formation. For instance, Huang et al. demonstrated that astrocytes regulate cell distancing in peri-plaque glial nets via the Plexin-B1 receptor, which restricts microglial access to amyloid deposits, thereby affecting amyloid compaction (ref: Huang doi.org/10.1038/s41593-024-01664-w/). Furthermore, Eskandari-Sedighi et al. explored the role of CD33 isoforms in modulating microglial responses, revealing that different isoforms can skew microglial function and influence AD risk in a mouse model (ref: Eskandari-Sedighi doi.org/10.1186/s13024-024-00734-8/). Wasén et al. provided insights into the gut-brain axis by showing that Bacteroidota can inhibit microglial clearance of amyloid-beta, promoting plaque deposition in AD mouse models, thus linking gut microbiota to neuroinflammation (ref: Wasén doi.org/10.1038/s41467-024-47683-w/). These findings collectively underscore the complex interplay between microglia, astrocytes, and external factors such as gut microbiota in the progression of neurodegenerative diseases, suggesting potential therapeutic targets for intervention.

Microglial activation and inflammation are pivotal in various neurological conditions, including ischemic stroke and neurodegenerative diseases. Guan et al. highlighted the role of CMPK2 in promoting neuroinflammation and brain injury post-stroke, demonstrating that its expression is upregulated in microglia and monocytes, suggesting a potential target for therapeutic intervention (ref: Guan doi.org/10.1016/j.xcrm.2024.101522/). In the context of Parkinson's disease, Lee et al. found that SARS-CoV-2 infection exacerbates cellular pathology in dopaminergic neurons, indicating that viral infections can worsen neurodegenerative conditions by enhancing neuroinflammatory responses (ref: Lee doi.org/10.1016/j.xcrm.2024.101570/). Additionally, Patir et al. examined the heterogeneity of myeloid cells post-stroke, revealing that different microglial states contribute to the inflammatory response and tissue damage, emphasizing the need for targeted immunomodulatory strategies (ref: Patir doi.org/10.1016/j.celrep.2024.114250/). These studies collectively illustrate the dual role of microglia in both promoting and resolving inflammation, highlighting the complexity of their activation states and the potential for therapeutic modulation.

Microglia play a crucial role in the pathology of Alzheimer's disease (AD), particularly in the context of amyloid plaques. Mallach et al. utilized spatial transcriptomics to investigate microglia-astrocyte interactions within the amyloid plaque niche, revealing significant heterogeneity in cellular composition and signaling pathways that may influence plaque development (ref: Mallach doi.org/10.1016/j.celrep.2024.114216/). Wetering et al. further explored the relationship between neuroinflammation and AD co-pathology, noting that increased microglial activity correlates with higher pathology in limbic regions, suggesting that microglial responses are integral to the progression of AD (ref: Wetering doi.org/10.1186/s40478-024-01786-z/). Additionally, Henningfield et al. demonstrated that targeted modulation of plaque-associated microglia using hydroxyl dendrimers can effectively alter their inflammatory response, presenting a novel therapeutic approach to mitigate AD pathology (ref: Henningfield doi.org/10.1186/s13195-024-01470-3/). These findings underscore the importance of microglial dynamics in AD and highlight potential avenues for therapeutic intervention.

The gut-brain axis has emerged as a significant area of research in understanding neurodegenerative diseases, with microglia acting as key mediators. Herrera et al. demonstrated that IGF-1 gene therapy can prevent cognitive deficits and modulate neuroinflammation in a parkinsonism model, suggesting that gut-derived factors may influence microglial function and overall brain health (ref: Herrera doi.org/10.1016/j.bbi.2024.05.013/). Fang et al. provided evidence that prodromal intestinal inflammation exacerbates Parkinson's disease endophenotypes in a sex-dependent manner, indicating that gut health may significantly impact neuroinflammatory processes and microglial activation (ref: Fang doi.org/10.1038/s42003-024-06256-9/). These studies highlight the intricate relationship between gut health, microglial function, and neurodegenerative disease progression, suggesting that interventions targeting the gut microbiome could have therapeutic potential.

Microglial interactions with other cell types are critical for understanding their role in neuroinflammation and disease progression. Favret et al. investigated the impact of galactosylceramidase loss in oligodendrocytes and microglia on Krabbe disease, revealing that both cell types contribute to neuroinflammation and disease severity (ref: Favret doi.org/10.1016/j.ymthe.2024.05.019/). Additionally, Yan et al. found that knocking down TREM2 in microglia promotes a pro-inflammatory state and inhibits glioma progression, suggesting that microglial signaling pathways are vital for tumor microenvironments (ref: Yan doi.org/10.1186/s12964-024-01642-6/). Silva et al. explored the role of IL-10 in modulating astrocyte-mediated microglial activation in methamphetamine-induced neuroinflammation, highlighting the importance of cytokine signaling in regulating microglial responses (ref: Silva doi.org/10.1002/glia.24542/). These findings emphasize the complexity of microglial interactions with other cell types and their implications for neuroinflammatory diseases.

Environmental factors significantly influence microglial function and neuroinflammation. Morris et al. demonstrated that exposure to urban particulate matter impairs mitochondrial dynamics in microglial-like BV2 cells, suggesting that environmental pollutants can disrupt microglial health and function (ref: Morris doi.org/10.1113/JP285978/). Zheng et al. investigated the effects of interior decorative volatile organic compounds on sleep disorders, linking neuroinflammatory cascades to altered sleep patterns, which may involve microglial activation (ref: Zheng doi.org/10.1016/j.scitotenv.2024.173254/). Furthermore, Wickel et al. examined the effects of microglial depletion and repopulation on dendritic spine density, indicating that environmental factors can alter synaptic architecture through microglial activity (ref: Wickel doi.org/10.1002/glia.24541/). These studies highlight the critical role of environmental factors in shaping microglial responses and their potential impact on neurological health.

Therapeutic strategies targeting microglia are gaining attention for their potential to modulate neuroinflammation and improve outcomes in neurological diseases. Chauquet et al. provided evidence that exercise rejuvenates aged microglia and reverses T cell accumulation in the brain, suggesting that lifestyle interventions can positively impact microglial health and function (ref: Chauquet doi.org/10.1111/acel.14172/). Additionally, Beckers et al. highlighted the challenges in treating neuropathic pain due to the complex interplay of microglial activation and central sensitization, indicating that targeted therapies are needed to address these mechanisms (ref: Beckers doi.org/10.1186/s12974-024-03112-9/). Furthermore, Silva et al. explored the role of IL-10 in mitigating methamphetamine-induced neuroinflammation, suggesting that cytokine modulation could be a viable therapeutic approach (ref: Silva doi.org/10.1002/glia.24542/). These findings underscore the importance of developing targeted therapies that can effectively modulate microglial activity to improve neurological health.

Understanding the genetic and molecular mechanisms underlying microglial function is crucial for elucidating their roles in neurodegenerative diseases. Rahman et al. conducted a large-scale cognitive profiling study, identifying genetic factors associated with cognitive variability, which may inform future research on microglial involvement in neurodegeneration (ref: Rahman doi.org/10.1038/s41591-024-02960-5/). Wamsley et al. utilized single-nucleus RNA sequencing to uncover dysregulated gene regulatory networks in autism spectrum disorder, providing insights into the molecular underpinnings of microglial function in neurodevelopmental disorders (ref: Wamsley doi.org/10.1126/science.adh2602/). Additionally, Valenza et al. demonstrated that acute stress induces maladaptive responses in microglia and astrocytes, which can be rescued by ketamine administration, highlighting the potential for pharmacological interventions to modulate microglial responses (ref: Valenza doi.org/10.1038/s41398-024-02928-6/). These studies collectively emphasize the importance of genetic and molecular insights into microglial biology for developing targeted therapies.