Microglia, the resident immune cells of the central nervous system, exhibit a remarkable diversity in their states and functions, particularly during development and in response to injury. A study by Lawrence et al. revealed that microglia play a crucial role in maintaining structural integrity during fetal brain morphogenesis, highlighting their importance in early brain development (ref: Lawrence doi.org/10.1016/j.cell.2024.01.012/). In the context of brain injury, Lan et al. utilized a lineage tracing system to demonstrate the age-dependent plasticity of disease-associated microglia-like cells, showing that these cells can adapt their fate following injury, which is critical for recovery (ref: Lan doi.org/10.1016/j.immuni.2024.01.008/). Furthermore, Li et al. expanded on this by discussing the diversity and memory of disease-associated microglia (DAMs), revealing that their fate can vary significantly depending on the timing of the injury, with implications for therapeutic strategies (ref: Li doi.org/10.1016/j.immuni.2024.01.004/). These findings collectively underscore the dynamic nature of microglial responses and their potential for therapeutic targeting in various neurological conditions. Additionally, the role of microglia in neurodegenerative diseases has been further elucidated through studies examining ferroptosis, a form of regulated cell death. Liddell et al. demonstrated that microglial ferroptotic stress can lead to non-cell autonomous neuronal death, implicating microglial activation in the progression of neurodegenerative diseases like ALS (ref: Liddell doi.org/10.1186/s13024-023-00691-8/). This highlights the need for a deeper understanding of microglial functions and their interactions with neurons, particularly in the context of neuroinflammation and injury recovery. Overall, the research emphasizes the critical roles of microglia in both maintaining brain health and contributing to disease pathology.

Neuroinflammation is increasingly recognized as a key player in the pathogenesis of neurodegenerative diseases, with recent studies shedding light on its mechanisms and implications. Radke et al. conducted a comprehensive proteomic and transcriptomic profiling of brainstem tissues from individuals at various stages of COVID-19, revealing an inflammatory type I interferon response during the acute phase that resolves in later stages (ref: Radke doi.org/10.1038/s41593-024-01573-y/). This finding suggests that neuroinflammation may contribute to the cognitive impairments observed in COVID-19 patients, linking systemic inflammation to neurological outcomes. Furthermore, the study by Yildirim-Balatan et al. on Parkinson's disease highlighted how α-synuclein assemblies can activate microglia, promoting a neurotoxic phenotype that exacerbates neuroinflammation and neuronal damage (ref: Yildirim-Balatan doi.org/10.1186/s12974-024-03043-5/). In addition to these findings, Liddell et al. explored the role of microglial ferroptotic stress in neurodegeneration, demonstrating that this stress can trigger inflammatory cascades leading to neuronal death (ref: Liddell doi.org/10.1186/s13024-023-00691-8/). This work emphasizes the importance of understanding the interplay between microglial activation and neuronal health in the context of neurodegenerative diseases. Moreover, the study by Kjærgaard et al. provided evidence that cognitive dysfunction in metabolic dysfunction-associated steatotic liver disease is linked to systemic inflammation and neuroinflammation, further illustrating the widespread impact of inflammatory processes on cognitive health (ref: Kjærgaard doi.org/10.1016/j.jhepr.2023.100992/). Collectively, these studies underscore the critical role of neuroinflammation in neurodegeneration and highlight potential therapeutic targets for mitigating its effects.

Microglial activation is a central feature in various disease models, particularly in the context of neuroinflammation and neurodegeneration. Tang et al. investigated the challenges of drug delivery in ischemic stroke, emphasizing the need for innovative nanoplatforms that can penetrate the blood-brain barrier and target lesions effectively (ref: Tang doi.org/10.1002/adma.202312897/). This study highlights the importance of addressing microglial activation in stroke therapy, as activated microglia can contribute to both neuroprotection and neurotoxicity depending on their state. In parallel, Radke et al. provided insights into the neuroinflammatory responses observed in COVID-19, revealing significant changes in microglial activation patterns across different disease phases (ref: Radke doi.org/10.1038/s41593-024-01573-y/). Moreover, the research by Li et al. on the diversity and memory of DAMs in CNS diseases further illustrates the complexity of microglial responses in various pathological contexts (ref: Li doi.org/10.1016/j.immuni.2024.01.004/). This study indicates that microglial activation can have both beneficial and detrimental effects, depending on the timing and nature of the injury. Additionally, Liddell et al. explored how microglial ferroptotic stress can lead to non-cell autonomous neuronal death, suggesting that microglial activation is a critical factor in the progression of neurodegenerative diseases (ref: Liddell doi.org/10.1186/s13024-023-00691-8/). Overall, these findings emphasize the dual roles of microglia in disease models and the necessity for targeted therapeutic strategies that can modulate their activation states.

The interactions between microglia and other cell types are crucial for understanding the complex dynamics of neuroinflammation and neurodegeneration. Radke et al. highlighted the role of microglia in the context of COVID-19, where they interact with neurons and other glial cells, contributing to the inflammatory response observed in the brain (ref: Radke doi.org/10.1038/s41593-024-01573-y/). This study underscores the importance of examining microglial interactions with various cell types to fully understand the mechanisms underlying neurological symptoms in infectious diseases. Additionally, Li et al. provided insights into the diversity of DAMs and their interactions with other cell types in the CNS, revealing how these interactions can influence the fate of microglia and their roles in disease (ref: Li doi.org/10.1016/j.immuni.2024.01.004/). Furthermore, Liddell et al. explored how microglial ferroptotic stress can lead to non-cell autonomous neuronal death, indicating that microglial activation can have far-reaching effects on neuronal health (ref: Liddell doi.org/10.1186/s13024-023-00691-8/). This highlights the necessity of considering the microglial-neuronal axis in therapeutic approaches. The study by Tang et al. on ischemic stroke also emphasizes the importance of targeting microglial interactions with the blood-brain barrier and other cell types to enhance therapeutic efficacy (ref: Tang doi.org/10.1002/adma.202312897/). Collectively, these studies illustrate the intricate web of interactions between microglia and other cell types, which are essential for maintaining CNS homeostasis and responding to injury.

Therapeutic strategies targeting microglia are gaining traction as potential interventions for various neurological disorders. Radke et al. provided a comprehensive analysis of the inflammatory responses in the brain during COVID-19, suggesting that modulating microglial activation could be a viable therapeutic approach to alleviate neurological symptoms (ref: Radke doi.org/10.1038/s41593-024-01573-y/). This study highlights the potential for targeting microglial pathways to mitigate the effects of systemic inflammation on the CNS. Additionally, Tang et al. discussed the development of blood-brain barrier-penetrating nanoplatforms for ischemic stroke therapy, emphasizing the need for targeted delivery systems that can effectively modulate microglial responses at the site of injury (ref: Tang doi.org/10.1002/adma.202312897/). Moreover, the work by Li et al. on the TREM2 activator Hecubine demonstrates the potential for small molecules to directly influence microglial function and reduce neuroinflammation (ref: Li doi.org/10.1016/j.redox.2024.103057/). This study represents a promising avenue for developing therapeutics that can enhance microglial responses in neurodegenerative diseases. Furthermore, Liddell et al. highlighted the role of microglial ferroptotic stress in neuronal death, suggesting that targeting this pathway could provide a novel therapeutic strategy for neurodegenerative diseases (ref: Liddell doi.org/10.1186/s13024-023-00691-8/). Overall, these findings underscore the importance of developing targeted therapies that can modulate microglial activation and function to improve outcomes in various neurological conditions.

The role of microglia in cognitive impairment is an emerging area of research, with several studies linking neuroinflammation to cognitive deficits. Radke et al. highlighted the inflammatory responses in the brain during COVID-19, which may contribute to cognitive impairments observed in patients (ref: Radke doi.org/10.1038/s41593-024-01573-y/). This study suggests that targeting microglial activation could mitigate cognitive dysfunction associated with viral infections. Similarly, Kjærgaard et al. investigated cognitive dysfunction in metabolic dysfunction-associated steatotic liver disease, providing evidence that systemic inflammation and neuroinflammation lead to impaired memory and depression-like symptoms (ref: Kjærgaard doi.org/10.1016/j.jhepr.2023.100992/). Additionally, the study by Liddell et al. on microglial ferroptotic stress further emphasizes the connection between microglial activation and cognitive decline, as non-cell autonomous neuronal death can result from microglial responses to stress (ref: Liddell doi.org/10.1186/s13024-023-00691-8/). This highlights the need for a deeper understanding of how microglial interactions with neurons and other cell types can influence cognitive outcomes. Furthermore, the research by Li et al. on the diversity of DAMs indicates that the state of microglia can significantly impact cognitive health, suggesting that therapeutic strategies aimed at modulating microglial function may hold promise for addressing cognitive impairments in various neurological conditions (ref: Li doi.org/10.1016/j.immuni.2024.01.004/). Collectively, these studies underscore the critical role of microglia in cognitive impairment and the potential for targeted interventions to improve cognitive health.

Microglial responses to environmental factors are crucial for understanding their role in neuroinflammation and neurodegeneration. Radke et al. examined the impact of COVID-19 on microglial activation, revealing that environmental stressors associated with the virus can lead to significant inflammatory responses in the brain (ref: Radke doi.org/10.1038/s41593-024-01573-y/). This study highlights the importance of considering how external factors can influence microglial behavior and contribute to neurological symptoms. Additionally, Tang et al. discussed the challenges of drug delivery in ischemic stroke, emphasizing the need for therapeutic strategies that can effectively target microglial responses to environmental changes in the brain (ref: Tang doi.org/10.1002/adma.202312897/). Moreover, the work by Li et al. on the diversity of DAMs underscores the adaptability of microglia in response to various environmental cues, suggesting that their activation state can be influenced by the surrounding microenvironment (ref: Li doi.org/10.1016/j.immuni.2024.01.004/). This adaptability is critical for their role in maintaining homeostasis and responding to injury. Furthermore, Liddell et al. explored how microglial ferroptotic stress can lead to neuronal death, indicating that environmental stressors can have profound effects on microglial function and neuronal health (ref: Liddell doi.org/10.1186/s13024-023-00691-8/). Collectively, these studies emphasize the need to understand microglial responses to environmental factors to develop effective therapeutic strategies for neurodegenerative diseases.