Microglia, the resident immune cells of the central nervous system, originate from yolk sac progenitors and play crucial roles in brain development and homeostasis. Recent studies have highlighted the distinct developmental pathways of microglia and peripheral macrophages, particularly border-associated macrophages (BAMs). For instance, research by Utz et al. demonstrated that microglia and BAMs share a common lineage during early development, but their functional roles diverge significantly as they mature (ref: Utz doi.org/10.1016/j.cell.2020.03.021/). In contrast, Ydens et al. revealed that peripheral nerve macrophages (snMacs) arise from late embryonic precursors and are gradually replaced by bone marrow-derived macrophages, indicating a unique ontogeny that separates them from CNS microglia (ref: Ydens doi.org/10.1038/s41593-020-0618-6/). Furthermore, Fujita et al. explored the mechanisms by which microglia accumulate along axons, identifying the Netrin-G1 signaling pathway as critical for their axon-specific distribution and neuronal support during the postnatal period (ref: Fujita doi.org/10.1016/j.celrep.2020.107580/). These findings collectively underscore the complexity of microglial development and their adaptive functions in the CNS, setting the stage for understanding their roles in various neurological conditions. In addition to developmental insights, the functional implications of microglial activity have been further elucidated through studies examining their responses to pathological states. Ma et al. investigated the dynamics of soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF) as a biomarker for Alzheimer's disease, revealing that sTREM2 levels fluctuate in relation to Aβ and tau pathologies, suggesting a nuanced role for microglia in neurodegeneration (ref: Ma doi.org/10.1186/s13024-020-00374-8/). Hashikawa et al. contributed to the understanding of microglial spatial organization by profiling cell types within the habenula, a brain region implicated in motivated behaviors, thus linking microglial function to broader neurobehavioral contexts (ref: Hashikawa doi.org/10.1016/j.neuron.2020.03.011/). Overall, these studies highlight the multifaceted roles of microglia in both development and disease, emphasizing their importance in maintaining CNS integrity and responding to injury.

Microglia are increasingly recognized as key players in the pathophysiology of neurodegenerative diseases, particularly Alzheimer's disease (AD). Johnson et al. conducted a large-scale proteomic analysis of AD brains and cerebrospinal fluid, identifying early changes in energy metabolism associated with microglial and astrocytic activation, which may serve as potential therapeutic targets (ref: Johnson doi.org/10.1038/s41591-020-0815-6/). This study underscores the importance of understanding microglial activation states in the context of AD progression. In a related investigation, Ma et al. examined the role of TREM2 in AD, finding that alterations in sTREM2 levels correlate with Aβ and tau pathologies, further implicating microglial dysfunction in disease mechanisms (ref: Ma doi.org/10.1186/s13024-020-00374-8/). Moreover, Xu et al. explored the effects of elevated protein synthesis in microglia, linking it to autism spectrum disorders (ASD) and highlighting how dysregulated microglial function can lead to synaptic and behavioral aberrations (ref: Xu doi.org/10.1038/s41467-020-15530-3/). Benetatos et al. provided insights into the role of PTEN activation in tauopathy, demonstrating that microglial engulfment of synaptic structures is influenced by pathological tau, thus linking microglial activity to synaptic loss in neurodegenerative contexts (ref: Benetatos doi.org/10.1007/s00401-020-02151-9/). Collectively, these studies illustrate the complex interplay between microglial activation, synaptic integrity, and neurodegenerative disease progression, emphasizing the need for targeted therapeutic strategies that modulate microglial function.

Microglial activation is a critical component of the inflammatory response in various neurological conditions, including brain tumors and ischemic injury. Sarkar et al. demonstrated that niacin can reactivate dysfunctional microglia and macrophages in glioblastoma, suggesting a potential therapeutic avenue for enhancing antitumor immunity (ref: Sarkar doi.org/10.1126/scitranslmed.aay9924/). This study highlights the importance of reactivating myeloid cells to improve their functionality in the tumor microenvironment. In a different context, Li et al. investigated the role of cGAS in ischemic stroke, finding that inhibition of double-stranded DNA sensing ameliorates brain injury by reducing inflammatory responses, thereby linking microglial activation to neuroprotection (ref: Li doi.org/10.15252/emmm.201911002/). Further insights into microglial activation were provided by Jackson et al., who explored the relationship between diabetes and post-stroke cognitive impairment, revealing that microglial activation contributes to delayed neurodegeneration in diabetic stroke models (ref: Jackson doi.org/10.1186/s12974-020-01815-3/). Additionally, Zhao et al. examined the neuroprotective effects of USP8 in modulating microglial phenotypes during inflammation, demonstrating its potential to mitigate cognitive and motor deficits induced by lipopolysaccharide (ref: Zhao doi.org/10.1016/j.bbi.2020.04.052/). These findings collectively underscore the dual role of microglia in both promoting and resolving inflammation, highlighting their potential as therapeutic targets in various neurological disorders.

The therapeutic targeting of microglia has emerged as a promising strategy for addressing various neurological disorders. Bhat et al. investigated the effects of 1-[(4-nitrophenyl)sulfonyl]-4-phenylpiperazine (NSPP) on cognitive function following brain irradiation, demonstrating that NSPP preserves cognitive abilities in mouse models of glioblastoma without interfering with radiation therapy (ref: Bhat doi.org/10.1093/neuonc/). This study highlights the potential of pharmacological agents to modulate microglial activity and improve outcomes in cancer therapy. In another approach, Li et al. explored the neuroprotective effects of inhibiting the cGAS pathway in ischemic stroke, showing that this intervention can mitigate inflammatory responses and promote recovery (ref: Li doi.org/10.15252/emmm.201911002/). Moreover, Sharma et al. focused on dendrimer-mediated delivery of sinomenine to target activated microglia in traumatic brain injury, demonstrating that this strategy can effectively reduce neuroinflammation and improve recovery outcomes (ref: Sharma doi.org/10.1016/j.jconrel.2020.04.036/). These studies collectively emphasize the importance of developing targeted therapies that can modulate microglial function to enhance neuroprotection and improve recovery from neurological injuries. The ongoing exploration of microglial targeting strategies holds promise for advancing treatment options for a range of neurodegenerative and neuroinflammatory conditions.

Microglia play a pivotal role in maintaining synaptic health and function, with recent studies revealing their involvement in synaptic pruning and modulation. Benetatos et al. highlighted the activation of PTEN in tauopathy, showing that microglial engulfment of synaptic structures is influenced by pathological tau, linking microglial activity to synaptic loss (ref: Benetatos doi.org/10.1007/s00401-020-02151-9/). This finding underscores the importance of microglial function in synaptic integrity, particularly in the context of neurodegenerative diseases. Additionally, Savage et al. examined microglial interactions with synapses in a Huntington's disease model, revealing alterations in microglial morphology and phagocytic capacity that may contribute to synaptic dysfunction (ref: Savage doi.org/10.1186/s12974-020-01782-9/). Furthermore, Lau et al. investigated the effects of interleukin-33 on microglial transcriptome reprogramming in Alzheimer's disease, demonstrating that this cytokine can enhance microglial phagocytic activity and ameliorate Aβ pathology (ref: Lau doi.org/10.1016/j.celrep.2020.107530/). Xu et al. also contributed to this theme by linking elevated protein synthesis in microglia to autism spectrum disorders, suggesting that dysregulated microglial function can lead to synaptic and behavioral aberrations (ref: Xu doi.org/10.1038/s41467-020-15530-3/). Collectively, these studies highlight the critical role of microglia in synaptic function and their potential as therapeutic targets for restoring synaptic health in various neurological disorders.

Microglia are integral to the response to pain and injury, with their activation playing a crucial role in the development of neuropathic pain. Sarkar et al. demonstrated that niacin can reactivate dysfunctional microglia in glioblastoma, suggesting a potential therapeutic strategy for enhancing antitumor immunity while also addressing pain (ref: Sarkar doi.org/10.1126/scitranslmed.aay9924/). In a different context, Meng et al. investigated the role of EZH2 in neuropathic pain following brachial plexus avulsion, finding that increased EZH2 levels in microglia exacerbate pain by promoting inflammation (ref: Meng doi.org/10.1007/s12264-020-00502-w/). Additionally, Jackson et al. explored the relationship between diabetes and post-stroke cognitive impairment, revealing that microglial activation contributes to delayed neurodegeneration in diabetic stroke models (ref: Jackson doi.org/10.1186/s12974-020-01815-3/). Li et al. examined the effects of isobavachalcone on microglial activation, demonstrating its potential to inhibit neuroinflammation and alleviate pain responses (ref: Li doi.org/10.1016/j.freeradbiomed.2020.04.011/). These findings collectively underscore the dual role of microglia in mediating both protective and detrimental effects in pain and injury responses, highlighting their potential as therapeutic targets for managing pain and enhancing recovery.

Microglia have been shown to play complex roles in cancer biology, particularly in the context of glioblastoma. Maas et al. analyzed gene expression in microglia interacting with glioblastoma cells, revealing that these microglia downregulate genes involved in sensing and responding to tumor signals, which may facilitate tumor growth (ref: Maas doi.org/10.1186/s12974-020-01797-2/). This study highlights the potential for glioblastoma to hijack microglial functions to support its own progression. In a related study, Leardini-Tristão et al. investigated the effects of physical exercise on microglial activation and astrocyte coverage in a chronic cerebral hypoperfusion model, finding that exercise can normalize microcirculatory changes and reduce inflammation, suggesting a protective role for microglia in maintaining brain health (ref: Leardini-Tristão doi.org/10.1186/s12974-020-01771-y/). Furthermore, Rostami et al. identified astrocytes as potential antigen-presenting cells in the Parkinson's disease brain, indicating that the interplay between glial cells and immune responses may also extend to cancer biology (ref: Rostami doi.org/10.1186/s12974-020-01776-7/). Shaerzadeh et al. examined microglial senescence in the substantia nigra and ventral tegmental area, suggesting that aging-related changes in microglial function could influence neurodegenerative processes and potentially cancer susceptibility (ref: Shaerzadeh doi.org/10.1002/glia.23834/). Collectively, these studies underscore the multifaceted roles of microglia in cancer biology, emphasizing the need for further research to elucidate their contributions to tumor progression and therapeutic responses.

Microglial aging and senescence are critical areas of research, particularly in understanding their roles in neurodegenerative diseases. Shaerzadeh et al. demonstrated that microglial senescence occurs in both the substantia nigra and ventral tegmental area, highlighting the potential impact of aging on dopaminergic neuron support (ref: Shaerzadeh doi.org/10.1002/glia.23834/). This study suggests that increased microglial surveillance may be a compensatory response to aging-related neuronal loss. In a complementary study, Pan et al. conducted transcriptomic profiling of microglia and astrocytes throughout aging, revealing age-related gene expression changes that could contribute to neuroinflammation and cognitive decline (ref: Pan doi.org/10.1186/s12974-020-01774-9/). Moreover, Dos Santos et al. investigated microglial cell densities across various mammalian species, finding that microglial density is consistent across brain structures, which may have implications for brain function and aging (ref: Dos Santos doi.org/10.1523/JNEUROSCI.2339-19.2020/). Hung et al. explored the effects of DPP-4 inhibitors on microglial activation following traumatic brain injury, suggesting that these agents may have protective effects against neuroinflammation and promote recovery (ref: Hung doi.org/10.1096/fj.201902818R/). Collectively, these studies underscore the importance of understanding microglial aging and senescence in the context of neurodegenerative diseases, emphasizing their potential as targets for therapeutic interventions aimed at mitigating age-related cognitive decline.