Further studies have explored the differential regulation of granulin peptides derived from progranulin, which are implicated in microglial function and neuroinflammation (ref: Zhang doi.org/10.1186/s13024-021-00513-9/). The role of microglia in glioblastoma management was also examined, where arginine deprivation altered microglial polarity and enhanced the efficacy of radiotherapy, leading to improved survival outcomes in glioblastoma models (ref: Hajji doi.org/10.1172/JCI142137/). The interplay between microglial activation and visual deficits in autoimmune demyelinating diseases was highlighted in a study using the experimental autoimmune encephalomyelitis model, which demonstrated that microglial activity correlates with visual function changes (ref: Joly doi.org/10.1186/s12974-022-02416-y/). Overall, these studies emphasize the multifaceted roles of microglia in neuroinflammation and their potential as therapeutic targets.

Moreover, the study of compensatory macrophage activation in breast-to-brain metastasis revealed that targeting tumor-associated macrophages and microglia can lead to adaptive resistance against therapies, emphasizing the need for a nuanced understanding of microglial roles in cancer biology (ref: Klemm doi.org/10.1038/s43018-021-00254-0/). In the context of traumatic brain injury, enhancing endocannabinoid signaling in astrocytes was shown to promote recovery, indicating that microglial and astrocytic interactions are crucial for neuroprotection (ref: Hu doi.org/10.1093/brain/). Collectively, these studies illustrate the dual roles of microglia as both protectors and contributors to neurodegenerative processes, necessitating targeted therapeutic strategies.

Additionally, the study of neuropsychiatric lupus revealed that microglial reactivation precedes overt pathology, suggesting that early microglial changes could be linked to neurodevelopmental impairments (ref: Han doi.org/10.1038/s41392-021-00867-y/). The interplay between microglial activation and neurodevelopmental disorders underscores the importance of understanding microglial dynamics during critical periods of brain development. Overall, these findings suggest that targeting microglial function may offer new therapeutic avenues for addressing neurodevelopmental disorders.

Furthermore, the use of Prussian Blue Nanozyme as a pyroptosis inhibitor demonstrated its neuroprotective effects, suggesting that modulating microglial-mediated cell death pathways could be beneficial in neurodegenerative contexts (ref: Ma doi.org/10.1002/adma.202106723/). The activation of spinal cord microglia following peripheral nerve injury was shown to be critical for the development of chronic pain, linking microglial responses to long-lasting pain hypersensitivity (ref: Tansley doi.org/10.1038/s41467-022-28473-8/). These studies collectively highlight the complex and dynamic roles of microglia in responding to injury and their potential as therapeutic targets in various neurological conditions.

Moreover, the study of single-cell RNA sequencing revealed time- and sex-specific responses of spinal cord microglia to peripheral nerve injury, linking apolipoprotein E to chronic pain and highlighting the immune functions of microglia in pain pathways (ref: Tansley doi.org/10.1038/s41467-022-28473-8/). The findings collectively emphasize the importance of microglial responses in shaping immune dynamics within the CNS and their potential as therapeutic targets for modulating neuroinflammatory conditions.

Furthermore, the study of arginine deprivation in glioblastoma models demonstrated that altering microglial polarity can enhance the efficacy of radiotherapy, suggesting that metabolic interventions could be a viable therapeutic strategy (ref: Hajji doi.org/10.1172/JCI142137/). The exploration of immune modulation through microglial targeting, as seen in the context of neuropsychiatric lupus, underscores the potential for developing therapies that can effectively regulate microglial activity to mitigate disease progression (ref: Han doi.org/10.1038/s41392-021-00867-y/). Collectively, these studies indicate that targeted therapeutic approaches aimed at microglial function may offer new avenues for treating neurodegenerative and neuroinflammatory diseases.

Additionally, the investigation of neuronal NR4A1 deficiency in a mouse model of lupus revealed that microglial reactivation is associated with synaptic stripping, indicating that microglial activity may also influence tumor microenvironments and cancer progression (ref: Han doi.org/10.1038/s41392-021-00867-y/). The potential of microglia as therapeutic targets in cancer biology is further supported by studies exploring the modulation of their activity to improve treatment outcomes in glioblastoma and other malignancies. Overall, these findings underscore the importance of understanding microglial roles in cancer to develop effective therapeutic strategies.

Moreover, the investigation of pyroptosis inhibition through Prussian Blue Nanozyme revealed its neuroprotective effects, suggesting that modulating microglial-mediated cell death pathways could preserve synaptic function in neurodegenerative contexts (ref: Ma doi.org/10.1002/adma.202106723/). The differential regulation of granulin peptides derived from progranulin also points to the importance of microglial function in synaptic regulation and pathology (ref: Zhang doi.org/10.1186/s13024-021-00513-9/). Collectively, these studies emphasize the multifaceted roles of microglia in synaptic function and their potential as therapeutic targets for restoring synaptic health in various neurological disorders.