NeuroMolecular Medicine最新文献

{"title":"Therapeutic Potential of TUBB6 Inhibition for Hematoma Reduction, Microtubule Stabilization, and Neurological Recovery in an In Vivo Model of Intracerebral Hemorrhage.","authors":"Jun-Yao Huang, Qiang Ma, Ya-Jie Qi, Zhi-Yao Wang, Xiao-Guang Liu, Yi-Ming Zhu, Yu-Ping Li","doi":"10.1007/s12017-025-08838-0","DOIUrl":"https://doi.org/10.1007/s12017-025-08838-0","url":null,"abstract":"<p><p>This in vivo study explored the impact of TUBB6 inhibition in intracerebral hemorrhage (ICH), focusing on its effects on hematoma volume, microtubule stability, inflammation, neuronal preservation, and sensorimotor recovery. Sprague-Dawley rats was used to induce ICH by collagenase injection into the right striatum, followed by administration of TUBB6 antisense oligonucleotide (ASO) or Control ASO directly into the hematoma site 3 h post-ICH. Outcomes measured included hematoma volume, microtubule stability (acetylated α-tubulin), levels of inflammatory cytokines, mitogen-activated protein kinase (MAPK) pathway activity, neuronal degeneration (Fluoro-Jade C staining), and cell integrity (Cresyl Violet staining). Functional recovery was assessed using neurological severity scores (mNSS), corner turn, forelimb-placing, and rotarod tests, with body weight tracked for up to 28 days. TUBB6 expression increased with the severity of hemorrhage in the ICH models. TUBB6 ASO significantly reduced hematoma volume at 24- and 72-h post-ICH, restored acetylated α-tubulin levels, suppressed MAPK signaling pathway, and decreased pro-inflammatory markers with increased IL-10. TUBB6 ASO also reduced neuronal degeneration and improved cell viability. In terms of functional outcomes, the TUBB6 ASO + ICH group exhibited reduced mNSS scores, improved body weight maintenance, and better performance on corner turn, forelimb-placing and rotarod tests compared to the Control ASO + ICH group. TUBB6 ASO treatment demonstrated therapeutic potential in a rat model of ICH by reducing hematoma volume, stabilizing microtubules, modulating the MAPK signaling pathway, and mitigating inflammation. It also preserved neuronal integrity and enhanced sensorimotor recovery, suggesting its effectiveness as a therapeutic approach to improve ICH outcomes.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"15"},"PeriodicalIF":3.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468557","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":"The Role of Lactic Acid Bacteria in Improving Behavioral Deficits, Serum Levels of Vitamin D3, B12 and Reducing Oxidative Stress and Demyelination in a Cuprizone-induced Demyelination Model of Rat.","authors":"Maryam Kazemimiraki, Elham Moazamian, Mohammad Javad Mokhtari, Mehrdad Gholamzad","doi":"10.1007/s12017-025-08837-1","DOIUrl":"https://doi.org/10.1007/s12017-025-08837-1","url":null,"abstract":"<p><p>Multiple sclerosis constitutes a chronic, inflammatory, and demyelinating disorder affecting the central nervous system, with an estimated global prevalence of 2.5 million individuals. Emerging research underscores the significant influence of the gut microbiota on the immune system, suggesting a potential role in the initiation and progression of inflammatory diseases. This study investigated the potential therapeutic effects of Lactobacillus and Bifidobacterium species isolated from traditional dairy products on cuprizone-induced demyelination in a rat model. 48 adults male Wistar rats were randomly assigned to six groups. Demyelination was induced by daily oral administration of 0.6% (w/w) cuprizone mixed with food for 30 days. Subsequently, treated groups received oral administration of mixed of Lactiplantibacillus plantarum, Lactobacillus acidophilus, and Lactobacillus reuteri: and mixed of Bifidobacterium bifidum and Bifidobacterium animalis. A control group received no bacteria intervention. Behavioral deficits were assessed using grip-traction, beam-walking, and grid-walking tests. Oxidative stress biomarkers were quantified using colorimetric assays. The extent of demyelination was evaluated by hematoxylin and eosin staining of the corpus callosum. Serum levels of vitamin D₃ and B₁₂ were measured by ELISA. The results demonstrated that lactic acid bacteria supplementation significantly improved behavioral deficits and reduced demyelination in the corpus callosum. Furthermore, these bacteria administration was associated with reduced oxidative stress and increased serum levels of vitamin D₃ and B₁₂. These findings suggest that Lactobacillus and Bifidobacterium species may offer a supplementary therapeutic strategy for demyelinating disorders such as multiple sclerosis, potentially by mitigating oxidative stress, promoting remyelination, and enhancing vitamin D₃ and B₁₂ levels.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"14"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441468","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":"Time of the Day of Traumatic Brain Injury has Minimal Effects on Behavioral and Histological Outcomes in Mice of Both Sexes.","authors":"Charles K Davis, Soomin Jeong, Shruti Subramanian, Jeongwoo Choi, Carlie M Ostrom, Sena Park, Raghu Vemuganti","doi":"10.1007/s12017-025-08835-3","DOIUrl":"https://doi.org/10.1007/s12017-025-08835-3","url":null,"abstract":"<p><p>Transcription of > 50% of the mammalian coding genes follows circadian rhythm in an organ-specific manner. Recent findings highlighted the influence of time of the day in the progression of various neurological diseases and therapies. In the present study, we evaluated the effect of time of occurrence of traumatic brain injury (TBI) on behavioral and neuropathological outcomes in mice of both sexes. Following a controlled cortical impact injury induced between Zeitgeber time (ZT)1-4 or ZT13-16, behavioral deficits and brain damage were evaluated. There were no significant differences in post-TBI motor function between groups ZT1-4 and ZT13-16 in either male or female mice compared with the sex-matched naïve control. TBI-induced anxiety-like behavior was significantly higher in the female ZT13-16 cohort compared to the naïve cohort; but, no difference was observed between injured groups in both sexes. Similarly, spatial learning and memory were not significantly different between the ZT1-4 and ZT13-16 groups in both sexes. Post-TBI cortical lesion volume was also not significantly different between ZT1-4 and ZT-13-16 groups in both sexes. The present study observed no significant effects of occurrence time on TBI-induced brain damage or behavioral deficits in male and female mice.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"13"},"PeriodicalIF":3.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075273","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":"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}