Microglial activation plays a pivotal role in neuroinflammation, particularly in conditions like multiple sclerosis (MS). Berglund et al. demonstrated that microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation, highlighting the importance of microglial clearance of tissue debris in maintaining central nervous system (CNS) homeostasis (ref: Berglund doi.org/10.1126/sciimmunol.abb5077/). Similarly, Lowe et al. found that chronic alcohol consumption leads to microglial activation and peripheral macrophage infiltration in the CNS, emphasizing the role of the CCL2-CCR2 signaling axis in this process (ref: Lowe doi.org/10.1186/s12974-020-01972-5/). Furthermore, Fan et al. showed that inhibiting the HMGB1-RAGE axis can prevent the polarization of pro-inflammatory macrophages and microglia, providing neuroprotection after spinal cord injury (ref: Fan doi.org/10.1186/s12974-020-01973-4/). These studies collectively underscore the multifaceted roles of microglia in neuroinflammatory responses and their potential as therapeutic targets in neurodegenerative diseases. In addition to their role in neuroinflammation, microglia are also influenced by various transcription factors and cofactors. Mimouna et al. explored the role of GRIP1, a transcription cofactor, in modulating myeloid cell-driven neuroinflammation and response to IFN-β therapy in MS models, revealing its unexpected permissive role in neuroinflammation (ref: Mimouna doi.org/10.1084/jem.20192386/). Ren et al. identified Qki as an essential regulator of microglial phagocytosis during demyelination, where its depletion led to impaired phagosome formation and unresolved myelin debris, ultimately affecting axon integrity and remyelination (ref: Ren doi.org/10.1084/jem.20190348/). Whalley et al. further emphasized the coordination of repair processes by microglia, suggesting their critical involvement in CNS recovery mechanisms (ref: Whalley doi.org/10.1038/s41583-020-00399-4/). Together, these findings illustrate the complex interplay between microglial activation, transcriptional regulation, and neuroinflammatory processes.

Microglia are increasingly recognized for their roles in neurodegenerative diseases, including Alzheimer's disease (AD) and schizophrenia. McQuade et al. investigated the effects of TREM2 knockout on microglial responses in human models of AD, revealing significant gene expression and functional deficits that underscore the importance of TREM2 in modulating microglial activity (ref: McQuade doi.org/10.1038/s41467-020-19227-5/). Jadhav et al. further examined the impact of TREM2 mutations, specifically the Y38C variant, on neuronal synapses in adult mice, linking genetic variants to synaptic impairment and neurodegeneration (ref: Jadhav doi.org/10.1186/s13024-020-00409-0/). These studies highlight the critical role of microglia in the pathophysiology of AD and the potential for targeting TREM2-related pathways in therapeutic strategies. In the context of schizophrenia, Park et al. demonstrated that activated microglia disrupt metabolic pathways in developmental cortical interneurons derived from individuals with schizophrenia, leading to impaired mitochondrial function and synaptic development (ref: Park doi.org/10.1038/s41593-020-00724-1/). This suggests that prenatal immune activation may have lasting effects on neurodevelopment and contribute to the etiology of neuropsychiatric disorders. Additionally, De Boeck et al. identified IL-33 as a key cytokine in glioma progression, orchestrating an inflammatory microenvironment that exacerbates tumorigenesis (ref: De Boeck doi.org/10.1038/s41467-020-18569-4/). Collectively, these findings emphasize the dual role of microglia in both neurodegenerative diseases and cancer, suggesting that their modulation could have therapeutic implications across a range of conditions.

The role of microglia in cognitive function is increasingly recognized, particularly in the context of neurodevelopmental disorders such as Down syndrome (DS). Pinto et al. found that over-activated microglia in the Dp(16) mouse model of DS impair cognitive performance, indicating that microglial activation is detrimental to cognitive outcomes (ref: Pinto doi.org/10.1016/j.neuron.2020.09.010/). This study highlights the importance of microglial regulation in maintaining cognitive health and suggests that interventions targeting microglial activation could improve cognitive function in DS. Moreover, Wang et al. explored the mechanisms of myelination and axon regeneration, demonstrating that manipulating microglial activity can enhance myelination of regenerated axons (ref: Wang doi.org/10.1016/j.neuron.2020.09.016/). This finding underscores the potential for microglial modulation in promoting recovery following CNS injuries. Additionally, the studies by Berglund et al. and Ren et al. on microglial phagocytosis and neuroinflammation further support the notion that microglial health is crucial for cognitive function and recovery processes (ref: Berglund doi.org/10.1126/sciimmunol.abb5077/; ref: Ren doi.org/10.1084/jem.20190348/). Together, these studies illustrate the multifaceted roles of microglia in cognitive processes and their potential as therapeutic targets for cognitive impairments.

Microglia play a critical role in the immune response within the CNS, influencing both neuroinflammatory processes and neuroprotection. Chiot et al. demonstrated that modifying peripheral macrophages can alter microglial reactivity and extend survival in amyotrophic lateral sclerosis (ALS) models, suggesting a complex interplay between peripheral and central immune responses (ref: Chiot doi.org/10.1038/s41593-020-00718-z/). This highlights the potential for targeting peripheral immune pathways to modulate microglial activity and improve outcomes in neurodegenerative diseases. Fan et al. further explored the mechanisms underlying microglial polarization, showing that inhibiting the HMGB1-RAGE axis can prevent the activation of pro-inflammatory macrophages and microglia, thereby providing neuroprotection after spinal cord injury (ref: Fan doi.org/10.1186/s12974-020-01973-4/). Similarly, Lowe et al. found that chronic alcohol consumption leads to microglial activation and peripheral macrophage infiltration, emphasizing the role of the CCL2-CCR2 signaling axis in mediating these effects (ref: Lowe doi.org/10.1186/s12974-020-01972-5/). These findings collectively underscore the importance of microglial regulation in the immune response and suggest that targeting microglial activation could have therapeutic implications for various CNS disorders.

Microglia are essential for CNS injury responses and repair mechanisms. Matschke et al. investigated the neuropathological features of COVID-19 patients, revealing significant glial responses and inflammatory changes in the brain, which underscores the role of microglia in CNS pathology following viral infections (ref: Matschke doi.org/10.1016/S1474-4422(20)30308-2/). This highlights the importance of understanding microglial responses in the context of emerging infectious diseases and their potential impact on CNS health. Berglund et al. emphasized the critical role of microglial autophagy-associated phagocytosis in recovery from neuroinflammation, demonstrating that effective clearance of tissue debris is vital for restoring CNS homeostasis (ref: Berglund doi.org/10.1126/sciimmunol.abb5077/). Additionally, Fan et al. showed that inhibiting the HMGB1-RAGE axis can prevent detrimental microglial polarization and enhance neuroprotection after spinal cord injury (ref: Fan doi.org/10.1186/s12974-020-01973-4/). These studies collectively illustrate the multifaceted roles of microglia in CNS injury and repair processes, suggesting that therapeutic strategies aimed at modulating microglial activity could enhance recovery following CNS injuries.

Microglia are increasingly implicated in the pathogenesis of psychiatric disorders, with emerging evidence linking their activation to conditions such as major depressive disorder (MDD) and schizophrenia. Snijders et al. identified a distinct non-inflammatory signature of microglia in post-mortem brain tissue of patients with MDD, suggesting that aberrant immune processes may play a role in the disorder's pathogenesis (ref: Snijders doi.org/10.1038/s41380-020-00896-z/). This finding highlights the need for further investigation into the role of microglial function in MDD and the potential for targeting microglial activity in therapeutic interventions. In schizophrenia, Park et al. demonstrated that activated microglia disrupt metabolic pathways in developmental cortical interneurons, leading to impaired mitochondrial function and synaptic development (ref: Park doi.org/10.1038/s41593-020-00724-1/). This suggests that prenatal immune activation may have lasting effects on neurodevelopment and contribute to the etiology of neuropsychiatric disorders. Collectively, these studies emphasize the critical role of microglia in psychiatric disorders and suggest that modulating microglial activity could offer new therapeutic avenues for treatment.

Microglia are increasingly recognized for their role in metabolic disorders, particularly in the context of neurodegenerative diseases. Brekk et al. investigated lipid storage changes in Parkinson's disease (PD) patient brains, revealing distinct lipid distribution profiles among various cell types, including microglia (ref: Brekk doi.org/10.1073/pnas.2003021117/). This study underscores the importance of lipid metabolism in microglial function and its potential implications for neurodegenerative disease pathology. Additionally, Snijders et al. highlighted the role of aberrant immune processes in the pathogenesis of major depressive disorder (MDD), suggesting that microglia may play a key role in these processes (ref: Snijders doi.org/10.1038/s41380-020-00896-z/). The interplay between microglial activation and metabolic dysregulation may contribute to the development and progression of various neurodegenerative and psychiatric disorders. Together, these findings emphasize the need for further research into the metabolic functions of microglia and their potential as therapeutic targets in metabolic and neurodegenerative diseases.

Microglia are increasingly recognized for their roles in cancer, particularly in the context of glioblastoma. De Boeck et al. identified IL-33 as a key cytokine orchestrating the inflammatory brain tumor microenvironment, which contributes to glioma progression (ref: De Boeck doi.org/10.1038/s41467-020-18569-4/). This study highlights the dual role of microglia in tumorigenesis, suggesting that their modulation could impact glioblastoma outcomes. Moreover, the studies by Ren et al. and Mimouna et al. on microglial phagocytosis and neuroinflammation further support the notion that microglial health is crucial for maintaining a balanced tumor microenvironment (ref: Ren doi.org/10.1084/jem.20190348/; ref: Mimouna doi.org/10.1084/jem.20192386/). These findings collectively underscore the importance of understanding microglial interactions in cancer biology and suggest that targeting microglial activity could offer new therapeutic strategies for glioblastoma and potentially other cancers.