Neurodegenerative diseases such as multiple sclerosis (MS), Alzheimer's disease (AD), and Huntington's disease (HD) are characterized by complex interactions between inflammation, proteostasis, and neuronal integrity. A study on MS revealed that the immunoproteasome subunit PSMB8, induced by interferon-γ, disrupts proteasomal balance and reduces proteasome activity, contributing to neuronal dysfunction (ref: Woo doi.org/10.1016/j.cell.2025.05.029/). In the context of AD, the AMPK-ULK1 signaling pathway was found to be hampered, leading to mitochondrial dysfunctions that were alleviated by metformin treatment, highlighting potential therapeutic avenues (ref: Mary doi.org/10.1186/s13195-025-01772-0/). Furthermore, research into Huntington's disease identified down-regulation of neuroprotective protein kinase D, which may play a role in the selective vulnerability of striatal neurons to excitotoxicity (ref: Sebastián-Serrano doi.org/10.1038/s41419-025-07688-9/). The dynamics of α-synuclein aggregates in Parkinson's disease were also examined, revealing that different pathogenic structures induce distinct pathological changes in nonhuman primates, emphasizing the need for tailored therapeutic strategies (ref: Kinet doi.org/10.1126/sciadv.adu6050/). Overall, these studies underscore the multifaceted nature of neurodegeneration, where inflammation, metabolic dysregulation, and protein aggregation interplay to drive disease progression.

The exploration of molecular pathways in tumor biology has unveiled critical insights into pediatric low-grade gliomas and other malignancies. A study on KIAA1549::BRAF-fusion pediatric low-grade gliomas utilized a multi-omics approach to dissect MAPK-driven senescence, revealing therapeutic vulnerabilities that could be exploited for treatment (ref: Sigaud doi.org/10.1038/s41392-025-02279-8/). In a different context, the characterization of malignant rhabdoid tumors of cranial nerves highlighted their distinct clinical and molecular features, which are often overlooked in differential diagnoses (ref: Gruhle doi.org/10.1002/pbc.31823/). Furthermore, the development of a genetically controlled mouse model for high-risk sarcomas demonstrated the potential for creating diverse sarcoma types, facilitating better understanding and treatment of these complex tumors (ref: Imle doi.org/10.1038/s41467-025-60519-5/). Additionally, the loss of ATRX expression in adult gliomas was shown to extend beyond typical classifications, suggesting a broader spectrum of diagnostic implications (ref: Tauziède-Espariat doi.org/10.1186/s40478-025-02044-6/). Collectively, these findings emphasize the importance of molecular characterization in understanding tumor biology and developing targeted therapies.

Genetic and epigenetic factors play a pivotal role in the pathogenesis of various neurological disorders. A novel LRRK2 variant affecting RAB8A binding was identified in a family with Parkinson's disease, underscoring the significance of genetic variations in disease manifestation (ref: Vela-Desojo doi.org/10.1038/s41531-025-00989-y/). In synucleinopathies, abnormal α-synuclein was found to impair extracellular vesicle release through interactions with synaptotagmin 13, suggesting a mechanistic link between protein misfolding and synaptic dysfunction (ref: Miki doi.org/10.1186/s40035-025-00493-6/). Additionally, a study on atypical Parkinsonism highlighted the need for longitudinal follow-up to understand the progression and natural history of these disorders, which are influenced by genetic and environmental factors (ref: Yadav doi.org/10.1371/journal.pone.0325624/). Furthermore, the use of methylation analysis has emerged as a promising diagnostic tool for distinguishing between sweat gland tumors, emphasizing the relevance of epigenetic modifications in tumor classification (ref: Sohier doi.org/10.1111/his.15479/). These studies collectively illustrate the intricate interplay between genetic and epigenetic factors in shaping neuropathological outcomes.

Advancements in clinical and diagnostic approaches are crucial for improving outcomes in neuro-oncology and mental health. A study investigating the therapeutic effects of ketamine on depression identified a specific brain network associated with its efficacy, demonstrating the potential for targeted interventions in mood disorders (ref: Han doi.org/10.1016/j.biopsych.2025.06.006/). In pediatric brain tumors, ultra-low-input cell-free DNA sequencing was explored as a non-invasive method for tumor detection and characterization, addressing challenges related to low cfDNA yields in this population (ref: Fischer doi.org/10.1186/s40478-025-02024-w/). Additionally, automated diffusion analysis was employed to predict IDH genotype in gliomas, achieving performance comparable to manual assessments, which could streamline diagnostic processes (ref: Wu doi.org/10.3174/ajnr.A8776/). However, challenges remain in implementing the 2021 WHO CNS tumor classification in resource-limited settings, where access to molecular testing is limited, leading to diagnostic ambiguities (ref: Gilani doi.org/10.1093/nop/). These findings highlight the ongoing need for innovative diagnostic strategies and the importance of addressing disparities in healthcare access.

Neuroinflammation and immune responses are critical components in the pathology of neurodegenerative diseases and tumors. Research on Parkinson's disease demonstrated that distinct α-synuclein aggregates trigger differential pathological dynamics in nonhuman primates, highlighting the role of neuroinflammation in dopaminergic cell death (ref: Kinet doi.org/10.1126/sciadv.adu6050/). Additionally, a study on mucinous cystic neoplasms revealed that these tumors share a similar DNA methylation profile with mucinous ovarian tumors, suggesting a common origin and potential immune response mechanisms (ref: Leoni doi.org/10.1002/path.6439/). In the context of central neurocytoma, global DNA hypomethylation was identified as a hallmark feature associated with higher recurrence risk, indicating the relevance of epigenetic modifications in tumor behavior (ref: Krech doi.org/10.1007/s00401-025-02894-3/). Furthermore, the regulation of myogenesis by the mechanomiR-200c/FoxO3 axis was explored, revealing how mechanical stretch influences myoblast differentiation and proliferation, which may have implications for muscle regeneration and immune responses (ref: Mohamed doi.org/10.3390/cells14120868/). These studies collectively underscore the intricate relationship between neuroinflammation, immune responses, and disease progression.

Neurodevelopmental and pediatric disorders are characterized by unique molecular and clinical features that require specialized research approaches. The investigation of pediatric low-grade gliomas, particularly those with KIAA1549::BRAF fusions, utilized a multi-omics approach to uncover therapeutic vulnerabilities linked to oncogene-induced senescence (ref: Sigaud doi.org/10.1038/s41392-025-02279-8/). In the realm of synucleinopathies, abnormal α-synuclein was shown to impair extracellular vesicle release, which may contribute to synaptic dysfunction in pediatric populations (ref: Miki doi.org/10.1186/s40035-025-00493-6/). Additionally, malignant rhabdoid tumors of cranial nerves were identified as a distinct clinical entity, emphasizing the need for accurate diagnosis and treatment strategies in pediatric oncology (ref: Gruhle doi.org/10.1002/pbc.31823/). Furthermore, comparative analyses of tau oligomer interactomes in Alzheimer's disease and resilient individuals provided insights into protective mechanisms against neurodegeneration, highlighting the importance of understanding resilience in pediatric populations (ref: Jamison doi.org/10.1177/13872877251352382/). These findings illustrate the complexity of neurodevelopmental disorders and the necessity for targeted research and clinical approaches.

Brain imaging and functional studies have become integral to understanding neural mechanisms underlying various cognitive and clinical phenomena. A study on ketamine's therapeutic effects in depression identified a specific brain network linked to its efficacy, providing insights into the neurobiological underpinnings of mood disorders (ref: Han doi.org/10.1016/j.biopsych.2025.06.006/). Additionally, research on whole-brain modular dynamics demonstrated that resting-state brain network composition could predict sensorimotor learning performance, suggesting that neural architecture plays a crucial role in cognitive processes (ref: Standage doi.org/10.1162/netn_a_00420/). The generation of decellularized human brain tissue has also been explored as a novel approach to investigate cell-matrix interactions, which are essential for understanding neuroregenerative capacities (ref: Bueno doi.org/10.3389/fbioe.2025.1578467/). These studies collectively highlight the potential of advanced imaging techniques and functional analyses in elucidating the neural correlates of behavior and disease, paving the way for innovative therapeutic strategies.