CNS Neuroscience & Therapeutics最新文献

{"title":"METTL3 Increases Temozolomide Resistance in MGMT-Negative Glioblastoma by Enhancing CBX5 mRNA Stability in an m6A-IGF2BP2-Dependent Manner","authors":"Hui Deng,&nbsp;Ruoyu Chen,&nbsp;Daohong Qu,&nbsp;Cifu Qu,&nbsp;Jia Shi","doi":"10.1002/cns.71164","DOIUrl":"10.1002/cns.71164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We examined whether chromobox protein 5 (CBX5) contributes to temozolomide (TMZ) resistance in O⁶-methylguanine-DNA methyltransferase (MGMT)-negative glioblastoma (GBM) and whether it is regulated by methyltransferase-like 3 (METTL3)-dependent N⁶-methyladenosine (m⁶A) and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Public datasets, clinical specimens, MGMT-negative cells, and subcutaneous xenografts were examined using functional, mechanistic, and rescue assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the CGGA693 cohort of the Chinese Glioma Genome Atlas, higher CBX5 expression remained associated with shorter survival after multivariable adjustment (hazard ratio 1.178, 95% confidence interval 1.050–1.322; <i>p</i> = 0.005). CBX5 depletion increased TMZ sensitivity, apoptosis, and DNA damage, reduced ATM phosphorylation and RAD51 abundance, and restricted TMZ-treated xenograft growth; overexpression produced reciprocal effects in vitro. METTL3 depletion reduced CBX5 expression, mRNA stability, m⁶A enrichment, and wild-type reporter activity but did not significantly affect the m⁶A motif-mutant reporter. IGF2BP2 depletion reduced CBX5 protein and mRNA stability, whereas RNA immunoprecipitation supported an IGF2BP2–CBX5 mRNA association. CBX5 re-expression partially reversed METTL3 depletion-induced effects on viability and DNA damage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>METTL3-dependent m⁶A modification and IGF2BP2-associated stabilization help maintain CBX5 expression, contributing to TMZ resistance and ATM–RAD51-associated signaling in MGMT-negative GBM models.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Connectivity-Guided Individualized iTBS of the Posterior Parietal Cortex in Enduring Anorexia Nervosa: Network-Level Target Engagement and Multimodal Response in a Single Case.","authors":"Enrico Collantoni, Sofia Gentili, Arianna Menardi, Antonino Vallesi, Giovanni Librizzi, Elena Tenconi, Andrea Serino, Gaia Risso, Daniele Olivo, Fabio Sambataro, Angela Favaro, Valentina Meregalli","doi":"10.1002/cns.71206","DOIUrl":"https://doi.org/10.1002/cns.71206","url":null,"abstract":"<p><strong>Aims: </strong>Anorexia nervosa (AN) is a severe, often enduring disorder with scarce biological treatments, largely unable to address its core implicit features: habit-like food restriction and body-experience disturbances. We report a single-case application of resting-state connectivity-guided intermittent theta-burst stimulation (iTBS) to the posterior parietal cortex (PPC), a hub for body representation, peripersonal space, and affordance-based action.</p><p><strong>Methods: </strong>A 31-year-old woman with 12 years of treatment-resistant restricting AN, enrolled in an ongoing sham-controlled feasibility trial, underwent 20 active iTBS sessions to an individualized left-PPC site maximally coupled with a body-representation × affordance reference network, assessed at baseline, post-treatment, and four-month follow-up.</p><p><strong>Results: </strong>The protocol was fully feasible and well tolerated, without significant adverse events. Clinical change was gradual, with most of the weight gain occurring after the stimulation period: BMI rose from 15.65 to 16.01 at four-month follow-up and 16.40 over subsequent clinical follow-up. Blinded global improvement was minimal; anxiety fell below threshold, whereas eating-disorder and body-shape scores remained at floor. Target-reference connectivity increased in the a priori direction, toward the healthy-control mean. Exploratory measures changed heterogeneously, only partly tracking engagement.</p><p><strong>Conclusion: </strong>This case supports the feasibility and mechanistic plausibility of individualized parietal targeting in enduring AN, motivating a controlled trial to test its efficacy.</p><p><strong>Trial registration: </strong>The parent trial is registered on ClinicalTrials.gov (NCT07106645).</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71206"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PANoptosis In Microglia and Neurons Following Traumatic CNS Injury: A Systematic Review of Pathological Features and Therapeutic Implications.","authors":"Zhusheng Feng, Yingnan Fan, Tianshu Du, Peipei Huang, Yuqin Ye, Junjie Li","doi":"10.1002/cns.71208","DOIUrl":"10.1002/cns.71208","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) and spinal cord injury (SCI) induce PANoptosis, a pro-inflammatory programmed cell death modality orchestrated by the PANoptosome. This modality integrates pyroptosis, apoptosis, and necroptosis molecular machinery and contrasts with canonical single-pathway cell death.</p><p><strong>Methods: </strong>This systematic review (PROSPERO CRD420261383435) followed PRISMA and searched PubMed, Web of Science, and Cochrane Library. The in vivo studies confirming PANoptosis at the protein level were included; quality was assessed using CRIME-Q, and shared genes/protein interactions were analyzed via GeneCards, STRING, and Cytoscape.</p><p><strong>Results: </strong>Ten studies (five TBI and five SCI) were included. PANoptosis occurs in microglia and neurons, with significant crosstalk in secondary injury. Regulatory mechanisms included transcriptional regulation, inflammatory signaling, ubiquitination, energy metabolism, proteolysis, and mitophagy. Interventions comprised specific inhibitors, Chinese medicine formula granules, small molecules, siRNAs, drugs, metabolites, plasmids, and metal ions. Key sensors included ZBP1 and NLRP12, with ASC as the main adaptor; executioners included CASP1, GSDMD, CASP3/8, RIPK1/3, MLKL, and activated forms. Ischemia was the most significant disease-gene network factor.</p><p><strong>Conclusion: </strong>The primary injury activates microglia and neurons, inducing PANoptosis via multiple pathways; targeting PANoptosome assembly may preserve immuno-inflammatory balance and limit secondary damage. Future research should prioritize comprehensive PANoptosome detection, standardized animal models, CNS cell interactions, novel drug delivery, and ischemia-reperfusion injury.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71208"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fingolimod Alleviates Neuroinflammation and Blood-Brain Barrier Disruption in Epilepsy by Upregulating S1PR5 and Inhibiting the Rho/ROCK/NF-κB Pathway.","authors":"Chen Zhang, Yanli Duan, Mengmeng Ma, Lin Xu, Wei-Na Jin, Zhuoran Zhang","doi":"10.1002/cns.71212","DOIUrl":"10.1002/cns.71212","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to clarify the role of sphingosine-1-phosphate receptor 5 (S1PR5) in epileptic pathogenesis and the mechanism by which fingolimod exerts anti-epileptic effects, with a focus on neuroinflammation and blood-brain barrier (BBB) disruption.</p><p><strong>Methods: </strong>Multi-omics integration and machine learning were used to identify S1PR5 as a key candidate gene. Molecular docking was performed to verify the binding affinity between fingolimod and S1PR5. AAV-mediated S1PR5 overexpression was conducted in mouse hippocampi before kainic acid (KA) administration. KA-induced epileptic mice were randomly divided into control, model, and fingolimod intervention groups. Behavioral tests, qRT-PCR, Western blot, immunofluorescence, ELISA, and Evans Blue assay were used for evaluations.</p><p><strong>Results: </strong>S1PR5 expression was significantly downregulated in both epileptic patients and mouse hippocampi. Fingolimod bound stably to S1PR5 in silico. S1PR5 overexpression attenuated neuronal loss, microglial activation, and epileptic seizures in KA-treated mice, confirming that S1PR5 exerts protective effects in epilepsy. Fingolimod intervention upregulated S1PR5 expression, inhibited abnormal activation of the Rho/ROCK/NF-κB pathway, restored tight junction proteins (Claudin-5 and ZO-1), reduced BBB leakage, and lowered proinflammatory cytokines (TNF-α, IL-1β, IL-6). These changes were accompanied by alleviated seizure severity and frequency.</p><p><strong>Conclusion: </strong>S1PR5 serves as a protective regulator in epilepsy. Fingolimod exerts anti-epileptic effects by upregulating S1PR5, thereby inhibiting the Rho/ROCK/NF-κB pathway, reducing neuroinflammation, and preserving BBB integrity. These findings support S1PR5 as a promising target and provide a mechanistic basis for repurposing fingolimod in epilepsy therapy.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71212"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GFH312 Reduces Neuronal Death by Inhibiting RIPK1-Mediated Apoptosis and Necroptosis After Ischemic Stroke.","authors":"Ze Liu, Shengju Wu, Qian Suo, Chang Liu, Rubing Shi, Jing Ye, Haroon Khan, Jing-Yang Zhang, Yaohui Tang, Zhijun Zhang, Wanlu Li, Fu-Sheng Zhou, Guo-Yuan Yang","doi":"10.1002/cns.71053","DOIUrl":"10.1002/cns.71053","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the role of the RIPK1 inhibitor GFH312 in ischemic stroke and identify its potential mechanisms.</p><p><strong>Methods: </strong>GFH312 was administered to adult mice in an ischemic stroke model. To ascertain the effectiveness of treatment, neurobehavioral tests and assessments of brain damage were carried out. Brain tissues were examined using immunofluorescence as well as western blot and real-time quantitative PCR at various intervals following ischemia to evaluate inflammatory gene expression and signaling pathways linked to apoptosis and necroptosis.</p><p><strong>Results: </strong>Temporal analysis revealed that necroptosis and apoptosis were rapidly activated following ischemia, peaking at 1-3 days. GFH312 significantly improved neurological function and reduced brain injury in stroke mice. Mechanistically, GFH312 markedly inhibited apoptosis and necroptosis via suppression of the RIPK1-related signaling pathway (RIPK1-RIPK3-MLKL). In addition, GFH312 greatly decreased inflammatory gene expression in the brain.</p><p><strong>Conclusion: </strong>Apoptosis and necrotic apoptosis occur primarily during the acute poststroke phase. GFH312 exerts neuroprotective effects after ischemic stroke, which are associated with suppression of RIPK1-related apoptosis, necroptosis, and neuroinflammation.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71053"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-Exome Sequencing Reveals the Genetic Landscape and Genotype-Phenotype Spectrum of Dystonia in a Chinese Cohort.","authors":"Yiqing Gong, Huirong Peng, Zhao Chen, Jiawei He, Linliu Peng, Qian Jiang, Chunrong Wang, Linlin Wan, Lang He, Yuting Shi, Rong Qiu, Hong Jiang","doi":"10.1002/cns.71203","DOIUrl":"10.1002/cns.71203","url":null,"abstract":"<p><strong>Aims: </strong>To systematically characterize the genetic landscape of dystonia in a Mainland Chinese cohort, where over 60% of patients currently lack a molecular diagnosis due to limited large-scale genomic studies.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was performed in a cohort of 147 clinically diagnosed dystonia patients, with variants prioritized by population frequency, CADD/REVEL scores, and ACMG criteria; repeat expansion screening was also conducted to evaluate potential repeat-expansion phenocopies.</p><p><strong>Results: </strong>The overall diagnostic yield was 33.3%, with significantly higher rates in generalized and childhood-onset dystonia patients. We expanded the mutational and phenotypic spectra of established dystonia genes, including ATP1A3, KMT2B, GCH1, and TOR1A. Repeat expansion screening identified ATXN8OS and TBP expansions of uncertain clinical significance. Notably, two heterozygous FIG4 variants (c.1038_1039del and c.2181-2A>G) were identified as candidate findings requiring further validation. Exploratory HEK-293 T cell analyses showed that the frameshift variant produced a truncated protein and was associated with lysosome-related cellular alterations and reduced cell viability.</p><p><strong>Conclusion: </strong>This study delineates the genetic architecture and genotype-phenotype spectrum of dystonia in a Chinese cohort, providing population-specific evidence for the molecular classification and genetic evaluation of dystonia.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71203"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Treating Fields Enhance Temozolomide-Associated Growth Suppression in Glioblastoma Cells and Patient-Derived Organoids Through Cell-Cycle Blockade, Apoptosis, and SMAD-Associated Signaling.","authors":"Haiping Zhu, Yingbo Hou, Xuetao Li, Yi Tang, Zuoyu Jiang, Yang Zhang, Xuewen Zhang, Jiaming Du, Yang Zhu, Hanmiao Dong, Yeyang Xu, Ruoyu Sun, Chenyang Li, Zijian Han, Jian Lu, Lingzhi Xiong, Yulun Huang","doi":"10.1002/cns.71195","DOIUrl":"10.1002/cns.71195","url":null,"abstract":"<p><strong>Aims: </strong>Glioblastoma (GBM) remains difficult to treat despite multimodal therapy. Tumor Treating Fields (TTF) disrupts mitosis and provides clinical benefit in GBM, but the molecular responses associated with TTF and the effects of combining TTF with temozolomide (TMZ) remain incompletely defined.</p><p><strong>Methods: </strong>TMZ, TTF, and TMZ + TTF were evaluated in U251 and SHG140 GBM cells and patient-derived organoids. TTF was applied at 200 kHz and 1.75 V/cm RMS. Viability, colony formation, migration-related phenotypes, apoptosis, cell-cycle distribution, Western blotting, qRT-PCR, RNA-seq, and organoid morphology/immunofluorescence analyses were performed. SB525334 was used to assess SMAD-associated signaling.</p><p><strong>Results: </strong>Combined TMZ + TTF treatment more strongly suppressed cell viability, clonogenic growth, and migration-related phenotypes than either monotherapy, produced greater disruption of organoid structural integrity, and was accompanied by increased cleaved caspase-3 activation and apoptotic populations. RNA-seq identified TTF-associated transcriptomic changes involving chromatin-associated processes, DNA replication, and cell-cycle pathways. TTF was associated with selected SMAD-related signaling changes, G2/M accumulation, altered checkpoint signaling, and enhanced proapoptotic signaling. SB525334 partially attenuated TTF-associated SMAD phosphorylation, growth suppression, and cleaved caspase-3 induction.</p><p><strong>Conclusion: </strong>TTF enhances TMZ-associated antitumor responses in GBM cell lines and organoids, accompanied by cell-cycle blockade, apoptosis-associated changes, and selected SMAD-related signaling responses.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71195"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights Into the Role of Platelet Factor 4 in Neurodegenerative Diseases.","authors":"Qi Tian, Yanji Tong, Fang Yu, Xiaoming Hu","doi":"10.1002/cns.71118","DOIUrl":"10.1002/cns.71118","url":null,"abstract":"<p><strong>Background: </strong>As population aging accelerates worldwide, the prevalence and burden of neurodegenerative diseases (NDs) continue to rise, underscoring the urgent need to identify key molecular mechanisms driving disease progression and novel therapeutic targets. Chronic neuroinflammation is a hallmark of multiple NDs, including Alzheimer's disease and Parkinson's disease. Platelet factor 4 (PF4) is a chemokine primarily released by activated platelets and has traditionally been investigated for its roles in hemostasis, thrombosis, and peripheral inflammation.</p><p><strong>Results: </strong>Growing evidence has implicated PF4 in the pathogenesis of NDs. Altered PF4 expression has been observed across multiple NDs. As a central player at the intersection of the nervous, immune, and vascular systems, PF4 modulates inflammation, vascular homeostasis, and neuronal survival, all of which are critical in the pathogenesis of NDs. Dissecting the cell-type specific and temporally dynamic roles of PF4 across diverse disease contexts is essential for elucidating its contribution to neurodegenerative processes and disease progression.</p><p><strong>Conclusion: </strong>This review highlights PF4 as a potential mechanistic mediator in NDs and discusses its promise as both a biomarker and a therapeutic target. Further elucidation of PF4 signaling pathways may provide new insights into disease mechanisms and uncover novel opportunities for targeted interventions in NDs.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71118"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAF1 Promotes Gstt1-Mediated Ferroptosis by Promoting KDM1A Recruitment to Facilitate Pilocarpine-Induced Acute Seizure-Associated Neuronal Injury.","authors":"Tiantian Lu, Yonghong Feng, Xiuling Chen, Liyan Shen, Min Liu, Yanping Jia","doi":"10.1002/cns.71177","DOIUrl":"https://doi.org/10.1002/cns.71177","url":null,"abstract":"<p><strong>Background: </strong>Seizures can cause progressive neuronal damage. Our previous studies found that RAF1 mediates vitamin D's alleviation of seizures, but the mechanism by which RAF1 acts in seizures remains unclear.</p><p><strong>Methods: </strong>The pilocarpine-induced acute seizure-associated neuronal injury (Pilo-ASNI) model and glutamate-treated HT22 cells were used. Behavioral assessments were performed to evaluate seizure severity and latency; histopathological staining was performed to examine neuronal damage and survival; and cellular assays were performed to assess cell viability, cytotoxicity, and DNA damage. Transcriptome sequencing, Co-immunoprecipitation, molecular docking, ChIP-qPCR, and ferroptosis indicators were employed to elucidate the molecular mechanism.</p><p><strong>Results: </strong>RAF1 expression was markedly upregulated in the Pilo-ASNI model and glutamate-treated HT22 cells. RAF1 knockdown attenuated seizure severity and neuronal damage. Mechanistic studies in HT22 cells revealed that RAF1 inhibited Gstt1 transcription and promoted ferroptosis by promoting KDM1A recruitment and reducing H3K4me2 levels in the promoter region of Gstt1. Disrupting the RAF1-KDM1A interaction could inhibit ferroptosis and alleviate nerve damage, whereas Gstt1 knockdown reverses the protective effect of RAF1 inhibition.</p><p><strong>Conclusion: </strong>This study revealed a RAF1-driven pathway involving KDM1A-mediated epigenetic suppression of Gstt1 and subsequent ferroptosis, which may represent a potential target for neuroprotective intervention in seizures.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71177"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Residual Language Abilities Correlate With Diagnosis and Prognosis in Patients With Disorders of Consciousness.","authors":"Chuan Xu, Jiaxin Gao, Jing Zheng, Jie Yu, Jian Gao, Jingqi Li, Nai Ding, Benyan Luo","doi":"10.1002/cns.71176","DOIUrl":"10.1002/cns.71176","url":null,"abstract":"<p><strong>Background: </strong>Evaluating residual consciousness and predicting outcomes in unresponsive patients pose significant clinical challenges. Language assessment is crucial for these patients, and language-based EEG paradigms have shown promise in aiding diagnosis and prognosis in patients with disorders of consciousness (DoC). However, current language-based EEG paradigms either require higher-order cognitive functions, thereby misidentifying some conscious patients as unconscious, or rely on automatic processing, which fails to capture residual consciousness in DoC.</p><p><strong>Methods: </strong>Newly developed, simple phrase sequences combined with neural frequency tagging were used to explore a language paradigm tailored to a critical processing threshold. This paradigm was designed to reflect the dynamic process of consciousness in DoC, while requiring minimal cognitive load.</p><p><strong>Results: </strong>Our results showed that significant phrase-level EEG responses were observed in healthy subjects, MCS patients, and UWS patients in three conditions. Neural tracking of phrase structure showed a progressive decrease across three groups (healthy > MCS > UWS). Among the UWS patients, 52.38% (11 out of 21) and among the MCS patients, 45.83% (11 out of 24) exhibited significant ITPC at the syllable rate in at least one of the three conditions. Additionally, 38.10% (8 out of 21) of UWS patients and 33.33% (8 out of 24) of MCS patients demonstrated significant ITPC at the phrase rate. The language paradigm performance in this study was superior to that of other paradigms in detecting the proportion of residual language ability in DoC patients. Furthermore, cortical tracking at the phrase rate significantly correlated with 12-month outcomes and effectively classified patients according to their 12-month prognosis.</p><p><strong>Conclusions: </strong>The simplified language assessment demonstrates strong potential to detect residual language ability in DoC patients and could potentially be used to detect residual consciousness and determine prognosis in unresponsive patients.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71176"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}