Mitochondrial dysfunction plays a critical role in neuroinflammation and neurodegenerative diseases. Saller et al. demonstrated that acute suppression of mitochondrial ATP production can inhibit apoptosis while promoting NLRP3 inflammasome activation, highlighting the dual role of mitochondria in cell death pathways (ref: Saller doi.org/10.1016/j.immuni.2024.10.012/). This finding is significant as it suggests that targeting mitochondrial function could influence neuroinflammatory responses. In the context of COVID-19, Zhang et al. utilized spatial transcriptomics and proteomics to reveal brain-wide alterations in postmortem samples from patients, linking mitochondrial dysfunction to neurological symptoms observed after SARS-CoV2 infection (ref: Zhang doi.org/10.1038/s43587-024-00730-z/). Furthermore, Tu et al. identified that the NOTCH2NLC GGC intermediate repeat with serine insertion induces hypermyelination and mitochondrial dysfunction in mice, further supporting the connection between mitochondrial health and neuroinflammatory processes (ref: Tu doi.org/10.1186/s13024-024-00780-2/). Herzog et al. explored the relationship between neuroinflammation and suicidal ideation in depression, suggesting that TSPO binding may serve as a biomarker for vulnerability to stress-related mood changes, potentially linking mitochondrial dysfunction to psychiatric outcomes (ref: Herzog doi.org/10.1001/jamapsychiatry.2024.3543/). Lastly, Mayr et al. provided evidence of ferroptosis markers in Alzheimer's disease brains, indicating that mitochondrial dysfunction may contribute to neurodegeneration through ferroptotic pathways (ref: Mayr doi.org/10.1177/13872877241296563/). Together, these studies underscore the multifaceted role of mitochondrial dysfunction in neuroinflammation and neurodegenerative diseases, suggesting potential therapeutic targets for intervention.

The tumor microenvironment significantly influences glioma pathology and treatment responses. Lucas et al. conducted a comprehensive evaluation of IDH-wildtype glioblastoma, revealing molecular evolution and cellular phenotypes that correlate with differential treatment responses in a cohort of 106 patients (ref: Lucas doi.org/10.1093/neuonc/). This study highlights the importance of understanding the tumor microenvironment in tailoring therapeutic strategies. Laemmerer et al. further investigated diffuse hemispheric gliomas, specifically H3 G34R-mutant tumors, and found that alternative lengthening of telomeres renders these tumors hypersensitive to PARP inhibitor regimens, suggesting a unique interaction between telomere biology and treatment efficacy (ref: Laemmerer doi.org/10.1093/neuonc/). In the context of Neurofibromatosis Type 1, Lucas et al. also provided consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors, emphasizing the need for molecular stratification to improve diagnosis and treatment outcomes (ref: Lucas doi.org/10.1093/neuonc/). Ferrarese et al. explored the role of ZBTB18 in regulating cytokine expression and microglia/macrophage recruitment in glioblastoma, demonstrating how tumor-associated immune cells contribute to tumor progression (ref: Ferrarese doi.org/10.1038/s42003-024-07144-y/). Lastly, Tauziède-Espariat et al. characterized distinct radiological and histomolecular features of pediatric high-grade gliomas, revealing the influence of methylation-based subclasses on tumor behavior (ref: Tauziède-Espariat doi.org/10.1186/s40478-024-01881-1/). Collectively, these studies illustrate the complex interplay between glioma pathology and the tumor microenvironment, highlighting the potential for targeted therapies that consider these interactions.

Neurodegenerative diseases are characterized by complex mechanisms involving genetic, molecular, and environmental factors. Frattini et al. developed patient-derived midbrain organoids to study Lewy pathology formation in GBA1-associated Parkinson's disease, providing insights into the relationship between glucocerebrosidase mutations and α-synuclein aggregation (ref: Frattini doi.org/10.1093/brain/). This model offers a valuable tool for understanding the pathophysiology of Parkinson's disease and the role of genetic factors in disease progression. Nagata et al. investigated tau accumulation in Alzheimer's disease model mice, revealing alterations in microglial states that may contribute to neuroinflammation and neurodegeneration (ref: Nagata doi.org/10.1523/ENEURO.0260-24.2024/). This study highlights the importance of tau pathology in modulating immune responses in the brain. Additionally, Klinsing et al. demonstrated the feasibility of detecting somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients, suggesting a non-invasive approach to monitor disease progression and treatment response (ref: Klinsing doi.org/10.1186/s40478-024-01887-9/). These findings collectively emphasize the need for further research into the molecular mechanisms underlying neurodegenerative diseases, as well as the potential for innovative diagnostic and therapeutic strategies.

Molecular profiling and the identification of biomarkers are crucial for understanding and treating CNS disorders. Gangwar et al. explored the trapping of spermine and polyamine toxin blockers in GluK2 kainate receptor channels, highlighting the therapeutic potential of targeting ionotropic glutamate receptors in neurological disorders (ref: Gangwar doi.org/10.1038/s41467-024-54538-x/). This study underscores the importance of receptor modulation in the context of excitatory neurotransmission and its implications for conditions such as epilepsy and depression. Zipfel et al. conducted a retrospective study on malignant peripheral nerve sheath tumors, identifying perioperative factors that influence outcomes, which could inform clinical decision-making (ref: Zipfel doi.org/10.3390/cancers16223757/). Furthermore, Klinsing et al. demonstrated the detection of somatic copy number alterations from cerebrospinal fluid cell-free DNA, providing a promising avenue for non-invasive diagnostics in brain tumors (ref: Klinsing doi.org/10.1186/s40478-024-01887-9/). Tauziède-Espariat et al. characterized distinct features of pediatric high-grade gliomas, emphasizing the role of DNA methylation-based subtypes in tumor behavior and treatment response (ref: Tauziède-Espariat doi.org/10.1186/s40478-024-01881-1/). Together, these studies highlight the potential of molecular profiling and biomarkers in advancing our understanding of CNS disorders and improving patient outcomes.

Neuroinflammation has emerged as a significant factor in the pathophysiology of psychiatric disorders. Herzog et al. investigated the relationship between neuroinflammation, stress-related suicidal ideation, and negative mood in depression, finding that TSPO binding was associated with increased suicidal ideation during stress periods (ref: Herzog doi.org/10.1001/jamapsychiatry.2024.3543/). This suggests that neuroinflammatory markers may serve as indicators of vulnerability to stress-related mood disorders. Zhao et al. characterized the clinico-sero-pathological features of anti-Ha antisynthetase syndrome, revealing a high prevalence of muscle damage among patients with this condition, which may have implications for understanding the neuroinflammatory components of autoimmune disorders (ref: Zhao doi.org/10.1111/bpa.13319/). Kong et al. explored the neuroprotective effects of genetically modified E. coli secreting melanin in Parkinson's disease, highlighting the potential for microbiome-derived therapies in modulating neuroinflammation (ref: Kong doi.org/10.1186/s12951-024-02955-x/). Additionally, Ferrarese et al. demonstrated that ZBTB18 regulates cytokine expression in glioblastoma, affecting microglia/macrophage recruitment and potentially linking tumor-associated inflammation to psychiatric outcomes (ref: Ferrarese doi.org/10.1038/s42003-024-07144-y/). Collectively, these studies underscore the intricate relationship between neuroinflammation and psychiatric disorders, suggesting that targeting inflammatory pathways may offer new therapeutic strategies.

Understanding the cellular and molecular mechanisms underlying brain tumors is essential for developing effective treatments. Lucas et al. performed a longitudinal multimodal profiling of IDH-wildtype glioblastoma, revealing the molecular evolution and cellular phenotypes associated with different treatment responses in a large cohort of patients (ref: Lucas doi.org/10.1093/neuonc/). This comprehensive approach highlights the complexity of glioblastoma biology and the need for personalized treatment strategies. Laemmerer et al. investigated the interplay between telomere biology and treatment sensitivity in H3 G34R-mutant diffuse hemispheric gliomas, demonstrating that alternative lengthening of telomeres can enhance susceptibility to PARP inhibitors (ref: Laemmerer doi.org/10.1093/neuonc/). Furthermore, Lucas et al. provided consensus recommendations for the integrated diagnostic approach to peripheral nerve sheath tumors, emphasizing the importance of molecular stratification in improving diagnostic accuracy and treatment outcomes (ref: Lucas doi.org/10.1093/neuonc/). Ferrarese et al. explored the role of ZBTB18 in regulating cytokine expression and microglial recruitment in glioblastoma, shedding light on the tumor microenvironment's influence on tumor progression (ref: Ferrarese doi.org/10.1038/s42003-024-07144-y/). Lastly, Tauziède-Espariat et al. characterized distinct features of pediatric high-grade gliomas, linking methylation-based subtypes to clinical outcomes (ref: Tauziède-Espariat doi.org/10.1186/s40478-024-01881-1/). Together, these studies illustrate the multifaceted cellular and molecular mechanisms that drive brain tumor biology and underscore the potential for targeted therapies.

Extracellular vesicles (EVs) are increasingly recognized for their role in neurodegenerative diseases, serving as potential biomarkers and therapeutic targets. Matamoros-Angles et al. developed an efficient enzyme-free method for isolating brain-derived extracellular vesicles, addressing challenges associated with traditional isolation techniques that may compromise EV integrity (ref: Matamoros-Angles doi.org/10.1002/jev2.70011/). This advancement could facilitate the study of EVs in neurodegenerative contexts. Klinsing et al. demonstrated the detection of somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients, suggesting that cfDNA analysis could serve as a non-invasive diagnostic tool for monitoring tumor dynamics (ref: Klinsing doi.org/10.1186/s40478-024-01887-9/). Mayr et al. provided evidence of ferroptosis markers in Alzheimer's disease brains, linking mitochondrial dysfunction to neurodegeneration and highlighting the potential for targeting ferroptotic pathways in therapeutic strategies (ref: Mayr doi.org/10.1177/13872877241296563/). Together, these studies underscore the importance of extracellular vesicles and molecular markers in understanding neurodegenerative diseases and developing innovative diagnostic and therapeutic approaches.

Genetic and epigenetic factors play a crucial role in the development and progression of CNS tumors. Lucas et al. conducted a longitudinal study on IDH-wildtype glioblastoma, revealing the molecular evolution and cellular phenotypes that correlate with treatment responses, emphasizing the need for personalized approaches based on genetic profiling (ref: Lucas doi.org/10.1093/neuonc/). Laemmerer et al. investigated the impact of telomere biology in H3 G34R-mutant diffuse hemispheric gliomas, demonstrating that alternative lengthening of telomeres can enhance sensitivity to PARP inhibitors, suggesting a potential therapeutic target (ref: Laemmerer doi.org/10.1093/neuonc/). Furthermore, Lucas et al. provided consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors, highlighting the importance of incorporating molecular strata in the classification of tumors associated with Neurofibromatosis Type 1 (ref: Lucas doi.org/10.1093/neuonc/). Ferrarese et al. explored the role of ZBTB18 in regulating cytokine expression and microglial recruitment in glioblastoma, linking genetic factors to the tumor microenvironment's influence on tumor progression (ref: Ferrarese doi.org/10.1038/s42003-024-07144-y/). Tauziède-Espariat et al. characterized distinct features of pediatric high-grade gliomas, emphasizing the role of DNA methylation-based subtypes in tumor behavior and treatment response (ref: Tauziède-Espariat doi.org/10.1186/s40478-024-01881-1/). Collectively, these studies illustrate the intricate interplay between genetic and epigenetic factors in CNS tumors and their implications for diagnosis and treatment.