Glioblastoma multiforme (GBM) is characterized by its aggressive nature and the ability of glioma stem cells (GSCs) to evade immune responses. Gangoso et al. demonstrated that GSCs acquire myeloid-affiliated transcriptional programs through epigenetic immunoediting, leading to the establishment of an immunosuppressive tumor microenvironment that facilitates immune evasion (ref: Gangoso doi.org/10.1016/j.cell.2021.03.023/). This finding underscores the complexity of GBM's interaction with the immune system and highlights potential targets for immunotherapy. Additionally, Brooks et al. identified that the white matter serves as a pro-differentiative niche for glioblastoma, where tumor cell differentiation is influenced by the upregulation of SOX10 in response to white matter injury (ref: Brooks doi.org/10.1038/s41467-021-22225-w/). This differentiation process is part of a feedback loop that may contribute to tumor progression and resistance to therapies. Furthermore, Li et al. explored the role of PI3Kγ inhibition in suppressing microglia and tumor-associated macrophage accumulation in the glioblastoma microenvironment, which significantly enhanced the response to temozolomide (TMZ) in murine models (ref: Li doi.org/10.1073/pnas.2009290118/). These studies collectively highlight the multifaceted interactions within the tumor microenvironment and suggest that targeting these pathways could improve therapeutic outcomes in GBM.

Research into neurodegenerative diseases has increasingly focused on identifying biomarkers that can aid in diagnosis and monitoring disease progression. Du et al. reviewed the role of α-synuclein as a potential biomarker for Parkinson's disease (PD), emphasizing its presence in Lewy bodies and the loss of dopaminergic neurons (ref: Du doi.org/10.3389/fnagi.2021.645996/). The review highlights the need for reliable biomarkers to differentiate PD from other neurodegenerative disorders. In a different approach, Hül's study found that differential methylation of the CLDN5 gene, which encodes a protein crucial for blood-brain barrier integrity, is associated with cognitive decline, suggesting an early role for this gene in Alzheimer's disease (ref: Hül's doi.org/10.1016/j.biopsych.2021.01.015/). This finding indicates that epigenetic changes may precede traditional pathological markers of Alzheimer's. Ozawa et al. demonstrated that photo-oxygenation can reduce amyloid-β levels in Alzheimer's disease model mice, enhancing microglial clearance of amyloid aggregates (ref: Ozawa doi.org/10.1093/brain/). These studies illustrate the potential of both genetic and epigenetic factors as biomarkers for neurodegenerative diseases, paving the way for novel therapeutic strategies.

The impact of COVID-19 on neurological health has garnered significant attention, particularly regarding the neuropathological effects of SARS-CoV-2. Thakur et al. presented findings from autopsies of 41 patients who died from COVID-19, revealing that while neurological symptoms were prevalent, primary infection of the brain was not a significant factor in mortality (ref: Thakur doi.org/10.1093/brain/). This suggests that secondary effects, such as systemic inflammation, may play a more critical role in neurological manifestations. Casagrande et al. investigated the presence of SARS-CoV-2 RNA in the retina and optic nerve, finding detectable subgenomic RNA, which raises concerns about the virus's potential to affect the central nervous system (ref: Casagrande doi.org/10.1136/bjophthalmol-2020-318618/). Additionally, Hoffmann et al. reported that mutations in SARS-CoV-2 acquired in mink reduced antibody-mediated neutralization, highlighting the evolving nature of the virus and its implications for public health (ref: Hoffmann doi.org/10.1016/j.celrep.2021.109017/). These studies underscore the complex interplay between COVID-19 and neurological health, emphasizing the need for ongoing research into the long-term effects of the virus on the nervous system.

Epigenetic modifications have emerged as critical factors in cognitive decline and neurodegenerative diseases. Hül's study on the CLDN5 gene revealed that differential methylation patterns are associated with cognitive trajectories, suggesting that early blood-brain barrier dysfunction may contribute to cognitive decline beyond traditional Alzheimer's disease pathologies (ref: Hül's doi.org/10.1016/j.biopsych.2021.01.015/). This finding highlights the potential of epigenetic markers in predicting cognitive outcomes. Trinkaus et al. provided insights into the molecular architecture of α-synuclein inclusions, which are characteristic of various neurodegenerative disorders, including Parkinson's disease (ref: Trinkaus doi.org/10.1038/s41467-021-22108-0/). Their work elucidates the cellular interactions involved in the formation of these inclusions, which may have implications for understanding disease mechanisms. Furthermore, Pages et al. discussed the integration of DNA methylation profiling into the diagnostic process for pediatric CNS tumors, demonstrating how epigenetic analyses can complement traditional histopathological methods (ref: Pages doi.org/10.3390/cancers13061377/). Collectively, these studies emphasize the importance of epigenetics in understanding cognitive decline and highlight the potential for epigenetic markers in clinical diagnostics.

Neuroinflammation plays a pivotal role in various neurological disorders, and understanding the underlying cellular mechanisms is crucial for developing effective therapies. Kim et al. investigated the thrombin receptor's role in astroglia-neuron trophic coupling and neural repair following spinal cord injury (ref: Kim doi.org/10.1002/glia.24012/). Their findings indicate that genetic blockade of the thrombin receptor improves sensorimotor coordination in mice, suggesting that targeting this pathway may enhance recovery after injury. In the context of gliomas, Lasica et al. examined the prognostic significance of molecular markers in WHO grade II and III gliomas, revealing that IDH1/2 mutations are associated with longer overall survival and progression-free survival (ref: Lasica doi.org/10.1016/j.wneu.2021.04.026/). This study underscores the importance of genetic factors in glioma prognosis and highlights the potential for personalized treatment strategies. Together, these studies illustrate the complex interplay between cellular mechanisms and neuroinflammation, providing insights that could inform future therapeutic approaches.

Innovative therapeutic strategies are essential for addressing the challenges posed by neurodegenerative diseases and brain tumors. Ozawa et al. demonstrated that photo-oxygenation can effectively reduce amyloid-β levels in Alzheimer's disease model mice, enhancing microglial clearance and presenting a promising avenue for treatment (ref: Ozawa doi.org/10.1093/brain/). This approach highlights the potential of biocompatible catalysts in facilitating the degradation of pathological proteins. Additionally, Kim et al. explored the therapeutic implications of thrombin receptor modulation in spinal cord injury, showing that genetic inhibition of this receptor can improve recovery outcomes (ref: Kim doi.org/10.1002/glia.24012/). Furthermore, Pages et al. discussed the integration of DNA methylation profiling into the diagnostic and therapeutic processes for pediatric CNS tumors, emphasizing how molecular insights can guide treatment decisions (ref: Pages doi.org/10.3390/cancers13061377/). These studies collectively illustrate the importance of innovative therapeutic strategies and the integration of molecular diagnostics in improving outcomes for patients with neurological disorders.

Genetic factors play a crucial role in the pathogenesis and prognosis of various neurological disorders. Li et al. investigated the impact of PI3Kγ inhibition on glioblastoma, finding that it suppresses microglia and tumor-associated macrophage accumulation, thereby enhancing the response to temozolomide in murine models (ref: Li doi.org/10.1073/pnas.2009290118/). This study highlights the potential of targeting specific genetic pathways to improve treatment efficacy in glioblastoma. Additionally, Trinkaus et al. provided insights into the molecular architecture of α-synuclein inclusions, which are significant in the context of neurodegenerative diseases like Parkinson's disease (ref: Trinkaus doi.org/10.1038/s41467-021-22108-0/). Their findings elucidate the cellular interactions involved in the formation of these inclusions, which may inform future therapeutic strategies. Lasica et al. further examined the prognostic significance of genetic markers in WHO grade II and III gliomas, revealing that IDH1/2 mutations correlate with improved survival outcomes (ref: Lasica doi.org/10.1016/j.wneu.2021.04.026/). These studies underscore the importance of genetic factors in understanding neuropathology and developing targeted therapies.

The classification and diagnosis of pediatric CNS tumors have evolved significantly, necessitating a comprehensive understanding of the latest developments in the field. Cotter et al. emphasized the importance of integrating molecular genetic features into the classification of pediatric brain tumors, as outlined in the 2021 WHO Classification of Tumours of the Central Nervous System (ref: Cotter doi.org/10.1177/10935266211007022/). This integration is crucial for accurate diagnosis and treatment planning. Viaene et al. further explored the unique characteristics of pediatric glial tumors, highlighting the significance of molecular profiles in distinguishing these tumors from their adult counterparts (ref: Viaene doi.org/10.1177/10935266211009101/). Additionally, Pages et al. discussed the implementation of DNA methylation profiling in pediatric neuropathology, showcasing its role in enhancing diagnostic accuracy for challenging CNS tumors (ref: Pages doi.org/10.3390/cancers13061377/). Funakoshi et al. investigated the clinical significance of CDKN2A homozygous deletion in IDH-wildtype glioblastoma, revealing its impact on overall survival in patients with unmethylated MGMT status (ref: Funakoshi doi.org/10.1002/cam4.3860/). Collectively, these studies highlight the dynamic landscape of pediatric CNS tumor classification and the critical role of molecular genetics in guiding diagnosis and treatment.