Neurodegenerative diseases, particularly multiple sclerosis (MS) and Alzheimer's disease (AD), are characterized by complex interactions between inflammation, proteostasis, and neuronal integrity. A study by Woo highlights the role of the immunoproteasome in MS, where the induction of the PSMB8 subunit by interferon-γ leads to impaired proteasomal function, resulting in reduced proteasome activity and subsequent neuronal damage (ref: Woo doi.org/10.1016/j.cell.2025.05.029/). In the context of repetitive head impacts, Saloner's research investigates the plasma proteome in individuals with chronic traumatic encephalopathy (CTE), revealing significant alterations compared to healthy controls and Alzheimer's patients, which may elucidate the biological mechanisms underlying RHI-related neurodegeneration (ref: Saloner doi.org/10.1186/s13024-025-00860-x/). Furthermore, Dourte's work emphasizes the olfactory epithelium as a critical site for tau propagation in AD, suggesting that olfactory impairment may serve as an early indicator of neurodegenerative processes (ref: Dourte doi.org/10.1007/s00401-025-02902-6/). The interplay between mitochondrial dysfunction and neuroinflammation in AD is further explored by Mary, who demonstrates that the AMPK-ULK1 signaling pathway is hampered in AD, leading to mitochondrial alterations that can be mitigated by metformin (ref: Mary doi.org/10.1186/s13195-025-01772-0/). He's study introduces a quinolinium molecule that alleviates neuropathological features of AD by targeting mitochondrial dysfunction and neuroinflammation, highlighting potential therapeutic avenues (ref: He doi.org/10.1016/j.brainres.2025.149804/). Collectively, these studies underscore the multifaceted mechanisms contributing to neurodegeneration and the potential for targeted interventions.

The landscape of tumor biology, particularly in pediatric low-grade gliomas and other CNS tumors, is evolving with the integration of multi-omics approaches and artificial intelligence. Sigaud's research on KIAA1549::BRAF-fusion pediatric low-grade gliomas reveals that MAPK-driven senescence and the senescence-associated secretory phenotype (SASP) play crucial roles in tumor biology, identifying therapeutic vulnerabilities through a comprehensive multi-omics analysis (ref: Sigaud doi.org/10.1038/s41392-025-02279-8/). In parallel, Manzl's study addresses the challenges of tumor classification in CNS pathology, demonstrating the utility of AI in standardizing diagnostic processes and achieving high concordance rates with established DNA methylation classes (ref: Manzl doi.org/10.1038/s43018-025-00971-w/). The investigation of ETMR by de Faria highlights the role of perivascular cells in supporting stem-like states and chemoresistance, revealing distinct cellular subpopulations that contribute to tumor heterogeneity (ref: de Faria doi.org/10.1038/s41467-025-60442-9/). Additionally, Wu's work on automated diffusion analysis presents a non-invasive method for predicting IDH genotypes in gliomas, achieving performance comparable to human observers (ref: Wu doi.org/10.3174/ajnr.A8776/). Tauziède-Espariat's findings on ATRX loss in gliomas further expand the understanding of genetic markers in tumor pathology, suggesting that ATRX loss may occur in atypical cases beyond the established classifications (ref: Tauziède-Espariat doi.org/10.1186/s40478-025-02044-6/). These studies collectively illustrate the advancements in molecular pathology and the potential for improved diagnostic and therapeutic strategies in CNS tumors.

Neuroinflammation and immune responses play pivotal roles in various neurological conditions, with recent studies shedding light on the underlying mechanisms. Zhang's research on MDA5, a cytoplasmic RNA sensor, reveals that USP8 governs MDA5 homeostasis, impacting innate immunity and autoimmunity. The study demonstrates that USP8 inactivation leads to MDA5 degradation, suppressing antiviral signaling and exacerbating autoimmune responses (ref: Zhang doi.org/10.1002/advs.202503865/). Han's investigation into the neural circuits affected by ketamine treatment for depression identifies a specific brain network linked to its therapeutic effects, emphasizing the importance of understanding neuroinflammatory pathways in mood disorders (ref: Han doi.org/10.1016/j.biopsych.2025.06.006/). Additionally, Dukhinova reviews the role of cerebellar microglia in neuroinflammation, highlighting their dual function in regulating neuronal activity and contributing to inflammatory responses, which may inform future therapeutic strategies targeting microglial functions (ref: Dukhinova doi.org/10.4103/NRR.NRR-D-24-00550/). Bueno's proof-of-concept study on decellularized human brain tissue provides insights into cell-matrix interactions and their implications for neuroregeneration, further emphasizing the significance of the extracellular matrix in modulating immune responses (ref: Bueno doi.org/10.3389/fbioe.2025.1578467/). Collectively, these studies underscore the intricate interplay between neuroinflammation, immune responses, and neurodegenerative processes, paving the way for novel therapeutic approaches.

Genetic and epigenetic factors are increasingly recognized as critical components in the pathogenesis of various neurological disorders. Vela-Desojo's study identifies a new LRRK2 variant associated with Parkinson's disease, emphasizing the role of genetic mutations in influencing disease progression and pathology (ref: Vela-Desojo doi.org/10.1038/s41531-025-00989-y/). Novello's research on poly-γ-glutamic acid demonstrates its neuroprotective properties against α-synuclein-induced cytotoxicity and inflammation in astrocytes, suggesting potential therapeutic applications for neurodegenerative diseases (ref: Novello doi.org/10.1016/j.ijbiomac.2025.145303/). Ranches explores the differential expression of non-coding RNAs during SARS-CoV-2 infection in bronchial epithelial cells, revealing their role in modulating apoptosis and cell proliferation, which may have implications for understanding viral pathogenesis in the context of neurological health (ref: Ranches doi.org/10.1016/j.omtn.2025.102559/). Furthermore, Sohier's work highlights the importance of methylation analysis in distinguishing between sweat gland tumors, underscoring the potential of epigenetic markers in diagnostic pathology (ref: Sohier doi.org/10.1111/his.15479/). Yadav's longitudinal study protocol on atypical parkinsonism aims to elucidate the genetic and environmental factors contributing to disease progression, reflecting the need for comprehensive approaches to understand the complexities of neurodegenerative disorders (ref: Yadav doi.org/10.1371/journal.pone.0325624/). Together, these studies illustrate the multifaceted role of genetic and epigenetic factors in neuropathology and their potential as targets for therapeutic intervention.

Environmental and developmental neurotoxicity is an area of growing concern, particularly regarding the impact of pollutants on neurological health. Cao's research investigates the neurodevelopmental effects of perfluorinated compounds, specifically PFOS, PFBS, and 6:2 Cl-PFESA, on zebrafish embryos. The study employs multi-omics approaches to elucidate the molecular mechanisms underlying neurotoxic effects at environmentally relevant concentrations, highlighting the need for further investigation into the implications of these compounds on human health (ref: Cao doi.org/10.1016/j.jhazmat.2025.138744/). Dhivakar's study on ultrasonic vocalizations in adolescent rats reveals the effects of maternal isolation on stress responses and memory, suggesting that early-life stressors can have lasting impacts on neurodevelopment and behavior (ref: Dhivakar doi.org/10.1016/j.neulet.2025.138275/). Additionally, Mary’s research on the AMPK-ULK1 cascade in Alzheimer's disease indicates that environmental factors may influence mitochondrial dysfunction, further complicating the relationship between environmental exposures and neurodegenerative processes (ref: Mary doi.org/10.1186/s13195-025-01772-0/). Bueno's work on decellularized human brain tissue provides a platform for studying cell-matrix interactions in the context of neurotoxicity, emphasizing the importance of understanding how environmental factors affect cellular behavior and regeneration (ref: Bueno doi.org/10.3389/fbioe.2025.1578467/). Collectively, these studies underscore the critical need to explore the effects of environmental toxins on neurodevelopment and the mechanisms by which they may contribute to neurological disorders.

Recent advances in clinical and diagnostic methodologies are transforming the landscape of neuropathology, particularly in the context of CNS tumors. Gilani's study highlights the challenges faced in implementing the 2021 WHO CNS tumor classification in resource-limited settings, where a significant proportion of tumors could not be assigned a diagnosis due to the lack of molecular testing, leading to diagnostic ambiguity (ref: Gilani doi.org/10.1093/nop/). Fischer's research on ultra-low-input cell-free DNA sequencing demonstrates its potential for tumor detection and characterization in pediatric brain tumors, addressing the challenges of low cfDNA yields and paving the way for minimally invasive diagnostic approaches (ref: Fischer doi.org/10.1186/s40478-025-02024-w/). Mehanna's investigation into nickel sulfate toxicity in rats reveals neurobehavioral and neuropathological alterations, providing insights into potential protective strategies using curcumin supplementation, which may inform clinical practices for neurotoxic exposures (ref: Mehanna doi.org/10.1007/s12011-025-04654-6/). Dourte's work on the olfactory epithelium as a gateway for tau propagation in AD underscores the importance of early diagnostic indicators in neurodegenerative diseases (ref: Dourte doi.org/10.1007/s00401-025-02902-6/). These studies collectively reflect the ongoing efforts to enhance diagnostic accuracy and therapeutic strategies in neuropathology, emphasizing the integration of molecular and clinical insights.

The interplay between neural mechanisms and cognitive function is a critical area of research, particularly in understanding neurodegenerative diseases and their impact on cognition. Bueno's study on decellularized human brain tissue provides a novel platform for investigating cell-matrix interactions, which are essential for neuronal repair and regeneration, thereby influencing cognitive outcomes (ref: Bueno doi.org/10.3389/fbioe.2025.1578467/). He’s research on a quinolinium molecule demonstrates its potential to mitigate neuropathological changes in Alzheimer's disease through modulation of mitochondrial dysfunction and neuroinflammation, suggesting that targeting these pathways may enhance cognitive function in affected individuals (ref: He doi.org/10.1016/j.brainres.2025.149804/). Yadav's longitudinal study on atypical parkinsonism aims to elucidate the progression of cognitive decline in these syndromes, highlighting the need for comprehensive approaches to understand the etiology and cognitive implications of neurodegenerative disorders (ref: Yadav doi.org/10.1371/journal.pone.0325624/). Collectively, these studies emphasize the importance of understanding the neural mechanisms underlying cognitive function and the potential for therapeutic interventions to improve cognitive outcomes in neurodegenerative diseases.