Microglia play a crucial role in the regulation of neuroinflammation, particularly in the context of hypertension and neurodegenerative diseases. Recent studies have highlighted the involvement of microglia in sympathetic excitation during hypertensive challenges, where they act as early responders in the hypothalamic paraventricular nucleus (PVN) (ref: Wei doi.org/10.1016/j.immuni.2024.07.011/). In Parkinson's disease (PD), neuroinflammation exacerbates dopaminergic neuron loss, with a consistent correlation observed between neuroinflammation and neuron loss across various mouse models (ref: Bido doi.org/10.1126/scitranslmed.adm8563/). Furthermore, the antagonism of C5aR1 has been shown to suppress inflammatory glial responses in Alzheimer's disease, indicating a potential therapeutic target to reduce gliosis and memory deficits (ref: Schartz doi.org/10.1038/s41467-024-51163-6/). The role of microglia extends to polyG-dependent neurodegeneration in neuronal intranuclear inclusion disease, where the pathogenic mechanisms remain to be fully elucidated (ref: Zhong doi.org/10.1007/s00401-024-02776-0/). Additionally, IL-4 exposure has been found to enhance the anti-inflammatory properties of microglia, suggesting a complex interplay between microglial activation states and neuroprotection in PD (ref: Liu doi.org/10.1126/sciadv.adn4845/).

Neuroinflammation is a significant contributor to the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease and frontotemporal lobar degeneration. In Alzheimer's disease, amyloid-β-activated microglia have been shown to induce compound proteinopathies, leading to widespread tauopathy and synucleinopathy, which are critical features of the disease (ref: Lee doi.org/10.1093/brain/). The relationship between blood inflammation and neuroinflammation has been explored, revealing that peripheral inflammatory markers correlate with central inflammation and clinical outcomes in frontotemporal lobar degeneration (ref: Malpetti doi.org/10.1093/brain/). Furthermore, the regulation of astrocytic glycolysis-derived L-lactate production has been identified as a potential therapeutic strategy to rescue memory deficits and reduce amyloid burden in early Alzheimer's disease models (ref: Yang doi.org/10.1016/j.phrs.2024.107357/). In pediatric gliomas, immune profiling has identified TIM3 as a promising therapeutic target, highlighting the need for tailored immunotherapeutic strategies in childhood brain tumors (ref: Tripathi doi.org/10.1172/JCI177413/).

The interaction between microglia and other cell types is pivotal in understanding neuroinflammatory processes and their implications in various diseases. In the context of ischemic retinopathy, activated microglia have been shown to upregulate inflammatory gene expression in Müller cells, indicating a downstream effector role of these glial cells in the inflammatory response (ref: Zhou doi.org/10.1186/s12974-024-03190-9/). Additionally, the interplay between microglia and astrocytes has been highlighted in the regulation of dopaminergic neurotransmission in Alzheimer's disease, where astrocytic glycolysis impacts synaptic plasticity and Aβ aggregation (ref: Yang doi.org/10.1016/j.phrs.2024.107357/). The role of microglia in polyG-dependent neurodegeneration in neuronal intranuclear inclusion disease further emphasizes their interaction with neuronal populations and the complexity of neurodegenerative mechanisms (ref: Zhong doi.org/10.1007/s00401-024-02776-0/).

Microglia are integral to the immune response in the central nervous system, particularly in neurodegenerative diseases. The study of IL-4-driven microglial reactivity has revealed that this cytokine enhances the anti-inflammatory properties of microglia, which may ameliorate pathological features in Parkinson's disease (ref: Liu doi.org/10.1126/sciadv.adn4845/). Furthermore, the correlation between neuroinflammation and dopaminergic neuron loss in PD models underscores the importance of understanding the immune landscape within the brain (ref: Bido doi.org/10.1126/scitranslmed.adm8563/). The complexity of immune interactions in the brain suggests that targeting specific pathways could yield therapeutic benefits in managing neuroinflammatory conditions.

Emerging therapeutic strategies targeting microglia focus on modulating their activation states to achieve neuroprotection in neurodegenerative diseases. The antagonism of β-arrestins has been shown to influence IL-4-driven microglial reactivity, presenting a potential avenue for enhancing the neuroprotective effects of microglia in Parkinson's disease (ref: Liu doi.org/10.1126/sciadv.adn4845/). Additionally, engineered extracellular vesicle-based nanoformulations have been developed to coordinate neuroinflammation and immune homeostasis, enhancing therapeutic outcomes in Parkinson's disease (ref: Zhang doi.org/10.1021/acsnano.4c04674/). These strategies highlight the potential of targeting microglial pathways to mitigate neuroinflammation and improve neuronal health.

Microglial dynamics are critical in the context of brain injury, where their activation can lead to both protective and detrimental outcomes. The role of IL-4 in enhancing microglial reactivity suggests that manipulating microglial states could be beneficial in conditions like Parkinson's disease, where neuroinflammation plays a key role in disease progression (ref: Liu doi.org/10.1126/sciadv.adn4845/). Furthermore, the interplay between microglia and other immune cells in the brain, particularly in response to injury, underscores the need for a comprehensive understanding of microglial behavior in various pathological contexts (ref: Bido doi.org/10.1126/scitranslmed.adm8563/).

Microglia are increasingly recognized for their role in cognitive disorders, particularly in the context of neurodegenerative diseases. The modulation of microglial activity through cytokines such as IL-4 has been shown to enhance their neuroprotective properties, potentially alleviating cognitive deficits associated with diseases like Parkinson's (ref: Liu doi.org/10.1126/sciadv.adn4845/). Additionally, the relationship between neuroinflammation and cognitive impairment in Alzheimer's disease highlights the importance of targeting microglial pathways to improve cognitive outcomes (ref: Yang doi.org/10.1016/j.phrs.2024.107357/). The complex interactions between microglia and other cell types, including astrocytes and neurons, further complicate the landscape of cognitive disorders and emphasize the need for integrated therapeutic approaches.