Microglial activation plays a crucial role in neuroinflammation, particularly in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). In a comprehensive transcriptomic analysis of ALS spinal cord samples, researchers found increased expression of genes associated with microglia and astrocytes, while oligodendrocyte gene expression decreased, indicating a shift in glial dynamics (ref: Humphrey doi.org/10.1038/s41593-022-01205-3/). Another study highlighted the dual roles of hexokinase 2 in microglial function, showing that it regulates glycolytic flux and mitochondrial activity, essential for microglial responses to brain stimuli (ref: Hu doi.org/10.1038/s42255-022-00707-5/). Furthermore, hydroxychloroquine was linked to a reduced risk of AD among rheumatoid arthritis patients, suggesting that targeting the JAK/STAT pathway may mitigate neuroinflammation associated with AD (ref: Varma doi.org/10.1038/s41380-022-01912-0/). In spinal cord injury models, Treg cell-derived exosomes were shown to reduce microglial pyroptosis, promoting recovery, thus emphasizing the interplay between immune responses and microglial activation in neuroinflammatory contexts (ref: Xiong doi.org/10.1186/s12951-022-01724-y/).

Microglia are increasingly recognized for their role in neurodegenerative diseases, with studies revealing their involvement in aging and disease-specific pathologies. A high-resolution atlas of mouse brain aging demonstrated significant changes in non-neuronal cell types, particularly microglia, indicating their altered state during aging (ref: Allen doi.org/10.1016/j.cell.2022.12.010/). Research into ferroptosis, an iron-dependent cell death mechanism, showed that microglia are susceptible to this process, linking iron dysregulation to neurodegeneration in diseases like Parkinson's (ref: Ryan doi.org/10.1038/s41593-022-01221-3/). In the context of HIV, microglial activation was associated with changes in 3D genome organization, suggesting that viral infection can exacerbate neuroinflammatory responses (ref: Plaza-Jennings doi.org/10.1016/j.molcel.2022.11.016/). Additionally, novel microglial subtypes were identified in response to amyloid-beta and tau pathologies, highlighting the complexity of microglial responses in Alzheimer's disease (ref: Kim doi.org/10.1186/s13024-022-00589-x/).

The metabolic profile of microglia is crucial for their function and response to injury. A study demonstrated that hexokinase 2 is selectively expressed in microglia and plays a significant role in regulating their bioenergetics (ref: Hu doi.org/10.1038/s42255-022-00707-5/). Another investigation into microglial autophagy revealed that excessive activation of this pathway during demyelination leads to impaired myelin debris clearance, suggesting that modulating autophagy could enhance recovery from CNS injuries (ref: Zhou doi.org/10.1073/pnas.2209990120/). Furthermore, research on genetic expression changes in hyperhomocysteinemia indicated that older individuals exhibit significant alterations in microglial morphology and inflammatory gene expression, linking metabolic dysregulation to neuroinflammatory pathology (ref: Weekman doi.org/10.1002/trc2.12368/). These findings underscore the importance of metabolic pathways in shaping microglial responses and their implications for neurodegenerative diseases.

Microglia play a pivotal role in the immune response within the brain, particularly following ischemic events. Research has shown that T cells can modulate microglial responses to brain ischemia, highlighting the complex interplay between adaptive immunity and neuroinflammation (ref: Benakis doi.org/10.7554/eLife.82031/). Additionally, a study identified that aged lipid-laden microglia exhibit impaired responses to ischemic conditions, suggesting that age-related changes in microglial function can exacerbate stroke outcomes (ref: Arbaizar-Rovirosa doi.org/10.15252/emmm.202217175/). The exploration of pharmacological agents targeting neuroinflammation revealed that certain compounds can effectively modulate microglial activity, offering potential therapeutic avenues for CNS disorders (ref: Yim doi.org/10.1038/s12276-022-00903-z/). Furthermore, the role of SIRT5 in exacerbating microglia-induced neuroinflammation during ischemic stroke was elucidated, indicating that metabolic regulators can influence inflammatory pathways in microglia (ref: Xia doi.org/10.1186/s12974-022-02665-x/).

Microglia are essential for brain repair processes following injury, particularly in the context of demyelination and stroke. A study demonstrated that staged suppression of microglial autophagy enhances myelin debris clearance and promotes recovery in demyelination models, indicating that fine-tuning microglial activity can facilitate regeneration (ref: Zhou doi.org/10.1073/pnas.2209990120/). Additionally, the identification of novel microglial subtypes in response to amyloid-beta and tau pathologies suggests that microglia adapt their functions based on the specific disease context, which may influence recovery trajectories (ref: Kim doi.org/10.1186/s13024-022-00589-x/). Research into BDNF gene hydroxymethylation revealed that neuroinflammation can lead to depression-like behaviors, linking microglial activity to mood disorders and highlighting their role in both injury response and behavioral outcomes (ref: Zhao doi.org/10.1016/j.jad.2022.12.035/). These findings emphasize the dual role of microglia in both promoting repair and potentially contributing to adverse outcomes following brain injury.

Microglia are increasingly recognized for their role in synaptic plasticity and remodeling, particularly in the context of stress and neurodegenerative diseases. A study found that microglia-dependent excessive synaptic pruning leads to cortical underconnectivity and behavioral abnormalities following chronic social defeat stress, suggesting that microglial activity can significantly impact cognitive function (ref: Wang doi.org/10.1016/j.bbi.2022.12.019/). Another investigation revealed that the P2Y12 receptor mediates chronic stress-induced synapse loss in the prefrontal cortex, linking microglial signaling to stress-related cognitive deficits (ref: Bollinger doi.org/10.1038/s41386-022-01519-7/). Furthermore, targeting neuroinflammation through pharmacological agents has shown promise in protecting dopaminergic neurons and mitigating synaptic loss in models of Parkinson's disease, underscoring the therapeutic potential of modulating microglial function (ref: Sun doi.org/10.1038/s41401-022-01030-1/). These studies collectively highlight the critical role of microglia in synaptic health and their potential as therapeutic targets in neuropsychiatric disorders.

Aging significantly impacts microglial function and their role in neuroinflammation. Research has shown that aged lipid-laden microglia exhibit impaired responses to ischemia, which can worsen recovery outcomes in older individuals (ref: Arbaizar-Rovirosa doi.org/10.15252/emmm.202217175/). Additionally, a comprehensive study on brain aging revealed substantial changes in the cellular and molecular architecture of microglia, indicating that aging alters their functional states and responses to injury (ref: Allen doi.org/10.1016/j.cell.2022.12.010/). The relationship between BDNF gene hydroxymethylation and neuroinflammation-induced depression-like behaviors in aging mice further emphasizes the intricate connections between microglial activity, aging, and mood disorders (ref: Zhao doi.org/10.1016/j.jad.2022.12.035/). These findings collectively underscore the importance of understanding microglial changes with age to develop targeted interventions for age-related neurodegenerative diseases.