NeuroMolecular Medicine最新文献

{"title":"Seipin Deficiency Impairs Motor Coordination in Mice by Compromising Spinal Cord Myelination.","authors":"Hong Chen, Wenru Wang, Wenli Cui, Chuanyun Tu, Yuanyuan Han, Chengwu Zhang, Liu Yang, Xintao Huang, Qin Zhang, Li Lu","doi":"10.1007/s12017-025-08834-4","DOIUrl":"https://doi.org/10.1007/s12017-025-08834-4","url":null,"abstract":"<p><p>The integrity of the myelin sheath of the spinal cord (SC) is essential for motor coordination. Seipin is an endoplasmic reticulum transmembrane protein highly expressed in adipose tissue and motor neurons in the SC. It was reported Seipin deficiency induced lipid dysregulation and neurobehavioral deficits, but the underlying mechanism, especially in SC, remains to be elucidated. In present study, we found that Seipin and myelin basic protein (MBP) increased synchronously in SC of developmental stage of mice. Demyelination impaired motor coordination as well as MBP and Seipin expression, which were alleviated by remyelination. Moreover, Seipin deficiency impaired motor coordination of mice, accompanied by hypomyelination in spinal cord. Mechanistically, we further demonstrated that myelin content as labeled by Fluormyelin, myelin basic protein (MBP) was down-regulated by Seipin deficiency. Seipin deficiency led to reduction of myelin-forming oligodendrocytes (OLs) density in spinal cord. Notably, administration of rosiglitazone (RG), a classic PPARγ activator, successfully restored the phenotypes manifested by Seipin deficiency including reduced OLs density, hypomyelination, as well as motor dyscoordination. In summary, present study revealed that Seipin deficiency disrupted motor coordination by compromising myelination in SC, and RG treatment could rescue the phenotypes. This study throws light on the mechanism underlying Seipin deficiency associated disorders and paves ways for developing therapeutics toward those diseases.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"12"},"PeriodicalIF":3.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacopa monnieri Extract Diminish Hypoxia-Induced Anxiety by Regulating HIF-1α Signaling and Enhancing the Antioxidant Defense System in Hippocampus.","authors":"Upendra Kumar Meena, Akhilendra Kumar Maurya","doi":"10.1007/s12017-025-08833-5","DOIUrl":"https://doi.org/10.1007/s12017-025-08833-5","url":null,"abstract":"<p><p>Hypoxia is a significant stressor, and stabilized hypoxia-inducible factor-1α (HIF-1α) regulates the expression of numerous genes, leading to various biochemical, molecular, physiological and genomic changes. The body's oxygen-sensing system activates gene expression to protect brain tissues from hypoxia. Gamma-aminobutyric acid, an inhibitory neurotransmitter, regulates brain excitability during hypoxia through the activation of HIF-1 α. Herbal medicines have been widely used for managing various toxicological effects and disorders including hypoxia; however, the data on safety, efficacy and the molecular mechanisms that increase vulnerability or lethality against hypoxia are still lacking and urgently need to be investigated. The Current study aims to investigate how Bacopa monnieri extract (BME), specially CDRI-08 affects the hippocampus of mice subjected to conditions that simulate hypoxia. The pre and co-treatment of mice involved administrating BME (200 mg/kg BW) for 14 days, followed by exposure to CoCl₂ (40 mg/kg BW). BME decreased the levels of reactive oxygen species (ROS) and lipid peroxidation, while it increased the Gamma-aminobutyric acid receptor subunit-ɑ1 (GABAAR-ɑ1) level as well as the activity of antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). Furthermore BME reduced the levels of HIF-1α and its downstream targets glucose transporter-1 (GLUT-1) and erythropoietin (EPO) in the DG, CA1, and CA3 regions of hippocampus. Additionally, results obtained from the open field, elevated zero maze and plus maze tests indicate that BME restores anxiety caused by hypoxia. Together, these findings suggested that BME mitigates the harmful effects of oxidative stress and altered hypoxia related signaling in hippocampus; and may provide a basis for its therapeutic use in the recovery from hypoxia-led anxiety.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"11"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Gut to Brain: The Impact of Short-Chain Fatty Acids on Brain Cancer.","authors":"Mohamed J Saadh, Omer Qutaiba B Allela, Radhwan Abdul Kareem, Gaurav Sanghvi, Soumya V Menon, Pawan Sharma, Balvir S Tomar, Aanchal Sharma, Hayder Naji Sameer, Atheer Khdyair Hamad, Zainab H Athab, Mohaned Adil","doi":"10.1007/s12017-025-08830-8","DOIUrl":"https://doi.org/10.1007/s12017-025-08830-8","url":null,"abstract":"<p><p>The primary source of short-chain fatty acids (SCFAs), now recognized as critical mediators of host health, particularly in the context of neurobiology and cancer development, is the gut microbiota's fermentation of dietary fibers. Recent research highlights the complex influence of SCFAs, such as acetate, propionate, and butyrate, on brain cancer progression. These SCFAs impact immune modulation and the tumor microenvironment, particularly in brain tumors like glioma. They play a critical role in regulating cellular processes, including apoptosis, cell differentiation, and inflammation. Moreover, studies have linked SCFAs to maintaining the integrity of the blood-brain barrier (BBB), suggesting a protective role in preventing tumor infiltration and enhancing anti-tumor immunity. As our understanding of the gut-brain axis deepens, it becomes increasingly important to investigate SCFAs' therapeutic potential in brain cancer management. Looking into how SCFAs affect brain tumor cells and the environment around them could lead to new ways to prevent and treat these diseases, which could lead to better outcomes for people who are dealing with these challenging cancers.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"10"},"PeriodicalIF":3.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of IL6 Gene Polymorphisms and Neurological Disorders: Insights from Integrated Bioinformatics and Meta-Analysis.","authors":"Md Harun-Or-Roshid, Md Nurul Haque Mollah, Jesmin","doi":"10.1007/s12017-025-08831-7","DOIUrl":"https://doi.org/10.1007/s12017-025-08831-7","url":null,"abstract":"<p><p>Interleukin 6 (IL6) is an inflammatory biomarker linked to central and peripheral nervous system diseases. This study combined bioinformatics and statistical meta-analysis to explore potential associations between IL6 gene variants (rs1800795, rs1800796, and rs1800797) and neurological disorders (NDs) and brain cancer. The meta-analysis was conducted on substantial case-control datasets and revealed a significant correlation between IL6 SNPs (rs1800795 and rs1800796) with overall NDs (p-value < 0.05). The disease-stratified analysis of rs1800795 revealed significant correlations with Schizophrenia, Alzheimer's, and Parkinson's diseases (p-value < 0.05), while rs1800796 showed a substantial connection with Celiac disease (p-value < 0.05). The ethnicity-stratified analysis revealed noteworthy associations between rs1800795 in both Asians and Caucasians (p-value < 0.05), while rs1800796 showed significant associations across all ethnic groups analyzed (p-value < 0.05). Furthermore, integrated Bioinformatics analyses using GTEx and TCGA datasets highlighted IL6's involvement in NDs and its potential role in brain cancer. Specifically, IL6 SNPs (rs1800795 and rs1800797) showed a significant association with Glioma (p-value < 0.001). Copy number alterations and increased IL6 expressions were linked to cancer severity (p-value < 0.001) and hypoxia (p-value < 0.0001). Kaplan-Meier survival analysis demonstrated that elevated IL6 expression was strongly associated with decreased overall survival in brain cancer patients (p-value < 0.0001). In conclusion, this study identified notable correlations between IL6 SNPs and NDs, underscoring their potential as valuable prognostic biomarkers for various neurological conditions.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"9"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effects of Sodium Nitroprusside on CKD-Induced Cognitive Dysfunction in Rats: Role of CBS and Nrf2/HO-1 Pathway.","authors":"Zeinab Hamidizad, Mehri Kadkhodaee, Farzaneh Kianian, Mina Ranjbaran, Fatemeh Heidari, Behjat Seifi","doi":"10.1007/s12017-024-08828-8","DOIUrl":"https://doi.org/10.1007/s12017-024-08828-8","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a conceivable new risk factor for cognitive disorder and dementia. Uremic toxicity, oxidative stress, and peripheral-central inflammation have been considered important mediators of CKD-induced nervous disorders. Nitric oxide (NO) is a retrograde neurotransmitter in synapses, and has vital roles in intracellular signaling in neurons. This research aims to determine the effectiveness of NO in CKD-induced cognitive deficits by considering the nuclear factor-erythroid factor 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling pathway and the important roles of cystathionine beta-synthase (CBS, H2S producing enzyme). Forty rats were divided into four experimental groups: sham, five-sixth (5/6) nephrectomy (5/6Nx, CKD), CKD + NO donor (Sodium nitroprusside, SNP), CKD + SNP and a CBS inhibitor (amino-oxy acetic acid, AOAA). To assess the neurocognitive abilities, eleven weeks after 5/6Nx, behavioral tests (Novel object recognition test, Passive avoidance test, and Barnes maze test) were done. Twelfth week after 5/6Nx, blood urea nitrogen (BUN) and serum creatinine (sCr) levels, as well as the nuclear factor-erythroid factor 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) expression levels and neuronal injury in the hippocampus and prefrontal cortex were assessed. As predicted, the levels of BUN and sCr (both P < 0.001) and neuronal injury in the hippocampus (P < 0.001 for CA1; CA3; DG) and prefrontal cortex (P < 0.001) increased in CKD rats as well as 5/6Nx induced reduction of Nrf2 (both P < 0.001) /HO-1(P < 0.001; P < 0.01 respectively) pathway activity in the hippocampus and prefrontal cortex in CKD rats. Moreover, CKD leads to cognitive disorder and memory loss (Novel object recognition test (NOR) (P < 0.001), Passive avoidance test (PA) (P < 0.001) and Barnes maze (BA) (Escape latency (P < 0.001); Error (P < 0.001)). SNP treatment significantly improved Nrf2 (both P < 0.001) /HO-1 (P < 0.001; P < 0.05 respectively) pathways and neuronal injury (P < 0.001 for CA1; CA3; DG) in the hippocampus and prefrontal cortex in CKD rats as well as enhanced learning and memory ability in CKD rats. However, ameliorating effects of SNP on cognitive disorder (NOR (P < 0.05), PA (P < 0.001) and BA (Escape latency (P < 0.05); Error (P < 0.001)) and Nrf2 (P < 0.01; P < 0.001 in the hippocampus and prefrontal cortex respectively) /HO-1 (P < 0.05 in both) signaling pathway activity were nullified by CBS inhibitor and H2S reduction. In conclusion, this study demonstrated that NO improved CKD-induced cognitive impairment and neuronal death which is may be depended to CBS activity and endogenous H2S levels.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"8"},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HERC5/ISG15 Enhances Glioblastoma Stemness and Tumor Progression by mediating SERBP1protein stability.","authors":"Zhixiao Li, Rongjun Qian, Mengda Li, Juntao Li, Yongji Guo, Yuanhang Zhou, Chunxiao Ma","doi":"10.1007/s12017-024-08826-w","DOIUrl":"https://doi.org/10.1007/s12017-024-08826-w","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common malignant brain tumor, and has a low survival rate and a poor prognosis. Intensive studies of pathogenic mechanisms are essential for exploring therapeutic targets for GBM. In this study, the roles played by interferon-stimulated gene 15 (ISG15), HECT, RCC1-containing protein 5 (HERC5), and SERPINE1 mRNA binding protein 1 (SERBP1) in regulating GBM cell stemness were investigated. The real-time quantitative polymerase chain reaction (qPCR), western blotting (WB), and immunohistochemistry (IHC) were used to determine the expression levels of HERC5, ISG15, and SERBP1. Cell stemness was analyzed using a cell sphere formation assay. Colony formation and cell counting kit-8 (CCK-8) assays were performed to assess cell proliferation, Transwell assays used to evaluate cell migration and invasion, and flow cytometry was used to assess cell apoptosis after treatment with temozolomide. SERBP1 stability was assessed by a CHX chase assay. A co-immunoprecipitation (Co-IP) assay verified the binding of ISG15 and HERC5 onto SERBP1. Our results showed that HERC5 and ISG15 were highly expressed in GBM. HERC5 and ISG15 promoted the cell stemness of GBM, and increased cell proliferation, sphere formation, migration, invasion, and chemoresistance. Moreover, HERC5 and ISG15 played a synergistic role in promoting the cell stemness of GBM. We also found that HERC5/ISG15 promoted the stability of SERBP1, which also promoted the cell stemness of GBM. The tumor-promoting role of HERC5 and ISG15 was also confirmed in a subcutaneous xenograft tumor model. Collectively, HERC5/ISG15 was found to regulate GBM stemness and tumor progression by mediating SERBP1 protein stability. Our present study suggests a promising therapeutic target for GBM.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"7"},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Genes to Metabolites: HSP90B1's Role in Alzheimer's Disease and Potential for Therapeutic Intervention.","authors":"Cheng Huang, Ying Liu, Shuxin Wang, Jinjun Xia, Di Hu, Rui Xu","doi":"10.1007/s12017-024-08822-0","DOIUrl":"https://doi.org/10.1007/s12017-024-08822-0","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a prototypical neurodegenerative disorder, predominantly affecting individuals in the presenile and elderly populations, with an etiology that remains elusive. This investigation aimed to elucidate the alterations in anoikis-related genes (ARGs) in the AD brain, thereby expanding the repertoire of biomarkers for the disease. Using publically available gene expression data for the hippocampus from both healthy and AD subjects, differentially expressed genes (DEGs) were identified. Subsequent intersection with a comprehensive list of 575 ARGs yielded a subset for enrichment analysis. Machine learning algorithms were employed to identify potential biomarker, which was validated in an AD animal model. Additionally, gene set enrichment analysis was conducted on the biomarker and its interacting genes and microRNAs were predicted through online databases. To assess its biological functions, the expression of the marker was suppressed in an in vitro model to examine cell viability and inflammation-related indicators. Furthermore, following treatment with the inhibitor, the dysregulated metabolites in the hippocampus of the model mice were evaluated. Forty-seven ARGs were ultimately identified, with HSP90B1 emerging as a central marker. HSP90B1 was found to be significantly up-regulated in AD hippocampal samples and its inhibition conferred increased cell viability and reduced levels of inflammatory factors in amyloid β-protein (Aβ)-treated cells. A total of 24 differentially expressed metabolites were confidently identified between model mice and those with low HSP90B1 expression, with bioinformatics analysis shedding light on the molecular underpinnings of HSP90B1's involvement in AD. Collectively, these findings may inform novel insights into the pathogenesis, mechanisms, or therapeutic strategies for AD.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"6"},"PeriodicalIF":3.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imagine, Discover, Inspire: Proceedings of the 4th International Conference of the Trisomy 21 Research Society.","authors":"Lisi Flores-Aguilar, Eric D Hamlett, Paula Araya, Eugenio Barone, Anita Bhattacharyya, Maria Carmona-Iragui, Li Chan, Brad Christian, Alberto C S Costa, Floriana Costanzo, Laura Del Hoyo Soriano, Mara Dierssen, Evan E Eichler, Elizabeth Fisher, Matthew Galbraith, Sujay Ghosh, Sandra Gimenez, Faycal Guedj, Sandra Guidi, Maria Florencia Iulita, William Mobley, Maria Chiara Pelleri, Marie-Claude Potier, Karen R Rabin, Angela Rachubinski, Anne-Sophie Rebillat, Eric Rubenstein, Hannah Saternos, Lorena Sordo, Andre Strydom, Natalia Valle-Tamayo, Katherine A Waugh, Eugene Yu, Ella Zeldich, Jorge Busciglio, Elizabeth Head","doi":"10.1007/s12017-024-08824-y","DOIUrl":"10.1007/s12017-024-08824-y","url":null,"abstract":"<p><p>Down syndrome (DS) or trisomy 21 (T21) is present in a significant number of children and adults around the world and is associated with cognitive and medical challenges. Through research, the T21 Research Society (T21RS), established in 2014, unites a worldwide community dedicated to understanding the impact of T21 on biological systems and improving the quality of life of people with DS across the lifespan. T21RS hosts an international conference every two years to support collaboration, dissemination, and information sharing for this goal. In 2022, T21RS hosted an international conference in Long Beach, California, from June 9 to 12. The conference, attended by 483 people including scientists, families, self-advocates, and industry representatives from 17 countries, was a dynamic and interactive meeting that shared discoveries from international research teams. This summary highlights the scientific discoveries shared at the 4th T21RS meeting with the Imagine, Discover, Inspire theme.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"5"},"PeriodicalIF":3.3,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSUN2-Mediated RNA 5-Methylcytosine Modification of PTEN Regulates Cognitive Impairments of Mice with Sleep Deprivation and Autophagy Through PI3K/AKT Signaling.","authors":"Gangli Yan, Yan Xu, Xiaobin Xing, Shuyue Chen, Fengguang Li","doi":"10.1007/s12017-024-08823-z","DOIUrl":"https://doi.org/10.1007/s12017-024-08823-z","url":null,"abstract":"<p><p>Sleep deprivation (SD) impairs learning and memory. Investigating the role of epigenetic modifications, such as 5-methylcytosine (m⁵C), in SD is crucial. This study established an SD mouse model and assessed the mRNA levels of m⁵C-related genes in brain tissue to identify potential candidates. Results indicated a significant elevation of NSUN2 in the SD group. Behavioral assessments using the Morris water maze test revealed cognitive impairments. Notably, inhibiting NSUN2 markedly alleviated these cognitive deficits and reduced autophagy in SD mice. Mechanistically, NSUN2 inhibition led to a pronounced decrease in PTEN levels, and the m⁵C modification of PTEN, which was increased by SD, was significantly reduced following NSUN2 knockdown. It was found that NSUN2 stabilizes PTEN mRNA through methylation. In the SD group, PTEN protein levels were elevated, and this increase was counteracted by NSUN2 inhibition. Collectively, the upregulation of PTEN may diminish the beneficial effects of NSUN2 inhibition on cognitive function and autophagy in SD mice. This study suggests that targeting NSUN2 and PTEN could be a novel therapeutic approach to ameliorate cognitive impairments and autophagy associated with SD, offering a promising strategy for the clinical management of SD-related cognitive deficits.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"4"},"PeriodicalIF":3.3,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-6 Promotes Muscle Atrophy by Increasing Ubiquitin-Proteasome Degradation of Muscle Regeneration Factors After Cerebral Infarction in Rats.","authors":"Fangyu Chen, Juanjuan Fu, Hui Feng","doi":"10.1007/s12017-024-08825-x","DOIUrl":"10.1007/s12017-024-08825-x","url":null,"abstract":"<p><p>Muscle atrophy in pathological or diseased muscles arises from an imbalance between protein synthesis and degradation. Elevated levels of interleukin-6 (IL-6) are a hallmark of ischemic stroke and have been associated with muscle atrophy in certain pathological contexts. However, the mechanisms by which IL-6 induces muscle atrophy in the context of stroke remain unclear. To investigate these effects, we used a rat model of middle cerebral artery occlusion (MCAO) and an in vitro model with the C2C12 cell line to uncover potential molecular mechanisms underlying IL-6-induced muscle atrophy. Our findings revealed elevated protein and serum levels of IL-6, along with increased markers of muscle atrophy, in MCAO rats compared to sham controls. We also observed overactivation of protein ubiquitination pathways and downregulation of muscle regeneration markers in MCAO rats. Further analysis indicated that IL-6 contributes to increased muscle protein ubiquitination. Inhibition of IL-6 signaling led to a significant reduction in infarct size and improved neurological deficit scores. Targeting the IL-6/IL-6R signaling pathway presents a promising therapeutic approach to mitigate muscle atrophy in individuals affected by ischemic stroke.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"3"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}