Microglial activation plays a crucial role in neuroinflammation, particularly in the context of pain and neurodegenerative diseases. Tansley et al. demonstrated that microglia in the spinal cord dorsal horn degrade perineuronal nets (PNNs) following peripheral nerve injury, contributing to pain hypersensitivity. This finding highlights the dual role of microglia as both protectors and aggressors in the nervous system, where their activation can lead to detrimental outcomes such as chronic pain (ref: Tansley doi.org/10.1126/science.abl6773/). In Alzheimer's disease, Yan et al. explored the contribution of peripheral monocyte-derived cells to the pathology of amyloid plaques, revealing that these cells account for 6% of plaque-associated macrophages in aged mice, suggesting a complex interplay between different immune cell types in the brain (ref: Yan doi.org/10.1172/JCI152565/). Zhao's research further emphasizes the metabolic shifts in microglia, showing that activated microglia switch from oxidative phosphorylation to glycolysis, a change that may be leveraged for therapeutic interventions in Alzheimer's disease (ref: Zhao doi.org/10.1186/s13024-022-00541-z/). Ruan et al. identified key molecules involved in extracellular vesicle secretion from microglia, which are crucial for maintaining brain homeostasis and modulating immune responses (ref: Ruan doi.org/10.1016/j.celrep.2022.110791/). Additionally, Zhang's study on the epigenetic regulation of microglial innate immune memory suggests that microglia can retain long-term memory of inflammatory events, potentially influencing their response to subsequent insults (ref: Zhang doi.org/10.1186/s12974-022-02463-5/). The findings from these studies collectively underscore the multifaceted roles of microglia in neuroinflammation and their potential as therapeutic targets.

Microglia are increasingly recognized for their roles in neurodegenerative diseases, particularly Alzheimer's and Parkinson's diseases. Zhao's work on microglial lactate metabolism indicates that these cells can switch their energy production methods, which may be critical in the context of neurodegeneration (ref: Zhao doi.org/10.1186/s13024-022-00541-z/). Lu et al. further explored this by demonstrating that metabolic reprogramming in microglia is essential for the internalization and degradation of α-synuclein, a protein implicated in Parkinson's disease. Their findings suggest that enhancing microglial metabolism could improve phagocytic function and mitigate neurodegeneration (ref: Lu doi.org/10.1186/s12974-022-02484-0/). The study by Li et al. highlights the neuroinflammatory response in the spinal cord, showing that activation of noradrenergic neurons can reduce microglial activation and alleviate neuropathic pain, indicating a potential therapeutic pathway for managing pain associated with neurodegenerative conditions (ref: Li doi.org/10.1186/s12974-022-02489-9/). Sudwarts et al. identified BIN1 as a key regulator of microglial activation, linking its expression to proinflammatory responses and neurodegeneration, thus presenting another target for therapeutic intervention (ref: Sudwarts doi.org/10.1186/s13024-022-00535-x/). These studies collectively illustrate the complex interactions between microglial metabolism, activation, and their roles in neurodegenerative diseases, emphasizing the need for targeted therapies that modulate microglial function.

The role of microglia in cancer, particularly glioblastoma, is gaining attention due to their involvement in the tumor microenvironment. Yeo et al. utilized single-cell RNA sequencing to reveal significant changes in the immune landscape during glioblastoma progression, highlighting the protumorigenic nature of microglial activation (ref: Yeo doi.org/10.1038/s41590-022-01215-0/). Kumar et al. investigated the glioma-associated immune response, identifying factors that enhance T-cell effector function, which could be pivotal for developing immunotherapies (ref: Kumar doi.org/10.1158/1078-0432.CCR-21-2830/). Chen's review on the epigenetic changes in glioblastoma emphasizes how the inflammatory microenvironment can facilitate tumor progression by evading immune surveillance, suggesting that targeting these pathways could improve therapeutic outcomes (ref: Chen doi.org/10.3389/fimmu.2022.869307/). Sudwarts et al. also contributed to this theme by demonstrating that BIN1 regulates microglial activation in the context of neuroinflammation and cancer, further linking microglial function to tumor biology (ref: Sudwarts doi.org/10.1186/s13024-022-00535-x/). Collectively, these studies underscore the dual role of microglia in both supporting tumor growth and presenting opportunities for therapeutic intervention in glioblastoma.

Microglia are central to the immune response in the central nervous system, acting as the first line of defense against pathogens and maintaining homeostasis. Ruan et al. highlighted the role of activated microglia in releasing extracellular vesicles that modulate brain immunity, providing insights into the mechanisms by which microglia communicate with other cells in the immune system (ref: Ruan doi.org/10.1016/j.celrep.2022.110791/). Plasschaert et al. examined hematopoietic stem cell engraftment in the brain, revealing how different administration routes affect the biodistribution of genetically engineered microglia-like cells, which could have implications for gene therapy in neurodegenerative diseases (ref: Plasschaert doi.org/10.1016/j.ymthe.2022.05.022/). Barros et al. focused on S100B, an inflammatory molecule linked to demyelination in multiple sclerosis, exploring its potential as a therapeutic target to mitigate inflammatory damage (ref: Barros doi.org/10.1093/braincomms/). These studies collectively illustrate the importance of microglia in orchestrating immune responses within the CNS and their potential as targets for therapeutic strategies aimed at modulating inflammation.

The metabolic profile of microglia is crucial for their functionality and response to various pathological conditions. Zhao's research on microglial lactate metabolism suggests that metabolic shifts from oxidative phosphorylation to glycolysis are significant during neurodegenerative processes, indicating that targeting these metabolic pathways could provide therapeutic benefits in diseases like Alzheimer's (ref: Zhao doi.org/10.1186/s13024-022-00541-z/). Ruan et al. contributed to this theme by identifying key molecules involved in the secretion of extracellular vesicles from microglia, which are essential for maintaining brain homeostasis and modulating immune responses (ref: Ruan doi.org/10.1016/j.celrep.2022.110791/). The interplay between microglial metabolism and their functional roles in neuroinflammation and neurodegeneration is becoming increasingly evident, suggesting that understanding these metabolic pathways could lead to novel therapeutic strategies aimed at enhancing microglial function and improving outcomes in various neurological disorders.

Microglia play a significant role in brain development and aging, influencing neurodevelopmental processes and age-related neurodegeneration. While specific studies focusing solely on microglia in development and aging were not highlighted in the provided articles, the overarching theme of microglial function across the lifespan is evident in the context of neuroinflammation and neurodegeneration. The findings from other themes, particularly regarding microglial activation and metabolism, suggest that age-related changes in microglial function could contribute to the increased vulnerability of the aging brain to neurodegenerative diseases. Understanding how microglia adapt their roles during development and aging is crucial for developing interventions that could mitigate age-related cognitive decline and neurodegenerative diseases.

Microglia represent promising therapeutic targets for a range of neurological disorders due to their central role in neuroinflammation and immune responses. Ruan et al. identified critical molecules involved in the secretion of extracellular vesicles from microglia, which could be targeted to modulate their immune functions and restore homeostasis in the brain (ref: Ruan doi.org/10.1016/j.celrep.2022.110791/). The potential for targeting microglial metabolism, as discussed by Zhao, suggests that interventions aimed at enhancing microglial energy production could improve their phagocytic capabilities and overall functionality in neurodegenerative diseases (ref: Zhao doi.org/10.1186/s13024-022-00541-z/). Additionally, the exploration of S100B as a therapeutic target in multiple sclerosis by Barros highlights the potential for developing treatments that specifically modulate microglial activity to reduce inflammation and promote repair processes in the CNS (ref: Barros doi.org/10.1093/braincomms/). Collectively, these studies underscore the importance of microglia as therapeutic targets and the need for further research to develop effective strategies for modulating their activity in various neurological conditions.