Microglia play a crucial role in regulating neuroinflammation and synaptic remodeling, particularly in response to various neurological conditions. Recent studies have highlighted the crosstalk between microglia and astrocytes, emphasizing that while astrocytes are involved in synapse remodeling, they do not directly engulf synapses as microglia do. This mechanism is vital for adapting synaptic structures to changing sensory environments and is notably upregulated in disease contexts (ref: Faust doi.org/10.1016/j.cell.2025.08.023/). Furthermore, research has shown that rod-shaped microglia interact with neuronal dendrites to modulate cortical excitability during neurodegeneration, particularly in models of TDP-43-related diseases, where neuronal hyperactivity is observed early in disease progression (ref: Xie doi.org/10.1016/j.immuni.2025.08.016/). In the context of radiation-induced brain injury, the unique chronic neuroinflammatory response exacerbates neurodegenerative processes, although the precise mechanisms remain unclear (ref: Shang doi.org/10.1038/s41392-025-02375-9/). Additionally, cholesterol metabolic reprogramming in microglia has been identified as a key factor in sustaining chronic neuroinflammation post-stroke, with distinct microglial clusters exhibiting altered cholesterol metabolism (ref: Zhao doi.org/10.1038/s42255-025-01379-7/). The role of microglia in various disease states is further underscored by findings that link aberrant interferon responses to reactive microglia in specific genetic models (ref: Lacovich doi.org/10.1093/brain/). Overall, these studies collectively underscore the multifaceted roles of microglia in neuroinflammation and their potential as therapeutic targets in various neurological disorders.

Microglia are increasingly recognized for their pivotal role in neurodegenerative diseases, with recent research exploring various therapeutic strategies. The ketogenic diet has been shown to inhibit glioma progression by enhancing gut microbiota-derived butyrate production, which in turn activates microglia and promotes anti-tumor effects (ref: Chen doi.org/10.1016/j.ccell.2025.09.002/). In pediatric low-grade gliomas, a spatial map of immune populations revealed that myeloid cells, including microglia, dominate the tumor microenvironment, suggesting their significant involvement in tumor biology (ref: Andrade doi.org/10.1038/s41590-025-02268-7/). Furthermore, adult hippocampal neurogenesis is influenced by neuropsychiatric disorders, highlighting the interplay between microglial activity and neurogenesis in conditions such as depression and schizophrenia (ref: Márquez-Valadez doi.org/10.1016/j.stem.2025.08.010/). Innovative therapeutic approaches, such as multimodal nanoregulators, have been developed to restore neurovascular units after traumatic brain injury, demonstrating the potential for microglial modulation in recovery (ref: Zhang doi.org/10.1002/adma.202509444/). The establishment of the Neurolipid Atlas provides a comprehensive resource for understanding lipid alterations in neurodegenerative diseases, further emphasizing the need for targeted therapies that consider microglial function and metabolism (ref: Feringa doi.org/10.1038/s42255-025-01365-z/). Collectively, these findings illustrate the complex roles of microglia in neurodegenerative processes and the potential for therapeutic interventions that target their function.

Therapeutic strategies targeting microglia have gained traction in recent research, particularly in the context of aging and cognitive decline. One study demonstrated that senescent-like border-associated macrophages can influence cognitive aging through migrasome-mediated signaling, which activates microglia and promotes a senescent phenotype (ref: Hu doi.org/10.1038/s43587-025-00956-5/). This highlights the potential for targeting microglial senescence as a therapeutic avenue. Additionally, exosomes derived from induced neural stem cells have shown promise in promoting recovery from traumatic brain injury by modulating microglial activity, suggesting a versatile approach to treatment (ref: Li doi.org/10.1002/advs.202508574/). In the context of neurodegenerative diseases, the blockade of the DP1 receptor has been shown to attenuate microglial senescence and cognitive decline, indicating that modulating microglial activation can have significant effects on disease progression (ref: Liu doi.org/10.1111/acel.70228/). Furthermore, research into the inflammatory signatures of microglia in models of amyotrophic lateral sclerosis has revealed distinct transcriptomic changes that could inform future therapeutic strategies (ref: Gao doi.org/10.1002/glia.70084/). These studies collectively underscore the importance of targeting microglial function and metabolism in developing effective therapies for neurodegenerative diseases.

Microglia interact extensively with other cell types in the central nervous system, influencing various pathological processes. Recent research has shown that PU.1 can restore microglial dysfunction caused by C9ORF72 repeat expansions in neural organoids, suggesting that non-neuronal cells play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ref: Ljubikj doi.org/10.1093/brain/). Additionally, spatial crosstalk modeling of the tumor microenvironment has identified CCR5-mediated glia-to-glia signaling as a key regulator of brain metastatic progression, highlighting the complex interactions between glial cells and tumor cells (ref: Ahn doi.org/10.1158/0008-5472.CAN-25-0237/). In the context of ischemic retinopathy, sorting nexin 3 has been implicated in myeloid cell necroptosis, further illustrating the role of microglia in retinal angiogenesis (ref: Wang doi.org/10.1073/pnas.2426578122/). Moreover, microglia have been shown to contribute to bipolar depression through Serinc2-dependent phospholipid synthesis, indicating their involvement in mood disorders (ref: Wang doi.org/10.1073/pnas.2500116122/). These findings emphasize the multifaceted interactions between microglia and other cell types, which are crucial for understanding their roles in health and disease.

Microglia are integral to synaptic plasticity, influencing both synapse formation and elimination. Recent studies have utilized innovative techniques such as multicolor fate mapping to reveal the dynamics of microglial proliferation and their interactions following ischemic stroke, demonstrating that microglia exhibit polyclonal proliferation in response to injury (ref: Kikhia doi.org/10.1038/s41467-025-63949-3/). This proliferation is critical for the inflammatory response and subsequent synaptic remodeling. Additionally, the blockade of the DP1 receptor has been shown to mitigate cognitive decline associated with microglial senescence, suggesting that modulating microglial activity can enhance synaptic function and plasticity (ref: Liu doi.org/10.1111/acel.70228/). Furthermore, altered inflammatory signatures in C9ORF72-ALS models indicate that microglial dysfunction can disrupt synaptic homeostasis, further linking microglial health to synaptic integrity (ref: Gao doi.org/10.1002/glia.70084/). Collectively, these studies underscore the critical role of microglia in maintaining synaptic plasticity and their potential as therapeutic targets for enhancing cognitive function.

Microglia play a significant role in the tumor microenvironment, particularly in brain tumors such as gliomas. Recent studies have characterized the immune landscape of gliomas, revealing unique genotype-independent prognostic immune signatures across IDH-stratified gliomas, highlighting the importance of microglial and other immune cell interactions in tumor progression (ref: Sussman doi.org/10.1093/neuonc/). Additionally, spatial crosstalk modeling has identified CCR5-mediated signaling as a critical regulator of brain metastatic progression, emphasizing the role of glial cells in facilitating tumor growth and invasion (ref: Ahn doi.org/10.1158/0008-5472.CAN-25-0237/). Furthermore, therapeutic strategies targeting microglial inflammation have shown promise in improving outcomes in intracerebral hemorrhage models, indicating that modulating microglial activity can have significant therapeutic implications (ref: Ye doi.org/10.1016/j.jare.2025.09.012/). These findings collectively illustrate the complex interactions between microglia and tumor cells, underscoring the potential for targeting microglial function in brain tumor therapies.

The role of microglia in aging and cognitive decline has garnered significant attention, particularly in the context of neurodegenerative diseases. Research has shown that senescent-like border-associated macrophages can influence cognitive aging through migrasome-mediated signaling to microglia, promoting a senescent phenotype that exacerbates cognitive decline (ref: Hu doi.org/10.1038/s43587-025-00956-5/). Additionally, the blockade of the DP1 receptor has been demonstrated to attenuate microglial senescence and cognitive decline, highlighting the potential for therapeutic interventions targeting microglial activation in aging populations (ref: Liu doi.org/10.1111/acel.70228/). These studies suggest that microglial health is crucial for maintaining cognitive function in aging, and that interventions aimed at modulating microglial activity may offer new avenues for addressing age-related cognitive decline.

Microglial metabolism is intricately linked to their function and response to injury. Recent studies have demonstrated that microglia exhibit polyclonal proliferation in response to ischemic conditions, with implications for their metabolic reprogramming and inflammatory response (ref: Kikhia doi.org/10.1038/s41467-025-63949-3/). Furthermore, the blockade of the DP1 receptor has been shown to ameliorate microglial overactivation and senescence, suggesting that metabolic pathways in microglia can be targeted to enhance their functional capacity (ref: Liu doi.org/10.1111/acel.70228/). These findings underscore the importance of understanding microglial metabolism as a means to modulate their function in various neurological conditions, paving the way for novel therapeutic strategies.