NeuroMolecular Medicine最新文献

{"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}

{"title":"The Interplay Between Accumulation of Amyloid-Beta and Tau Proteins, PANoptosis, and Inflammation in Alzheimer's Disease.","authors":"Xianbo Zhuang, Jie Lin, Yamin Song, Ru Ban, Xin Zhao, Zhangyong Xia, Zheng Wang, Guifeng Zhang","doi":"10.1007/s12017-024-08815-z","DOIUrl":"10.1007/s12017-024-08815-z","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a common progressive neurodegenerative disorder, and the vast majority of cases occur in elderly patients. Recently, the accumulation of Aβ and tau proteins has drawn considerable attention in AD research. This review explores the multifaceted interactions between these proteins and their contribution to the pathological landscape of AD, encompassing synaptic dysfunction, neuroinflammation, and PANoptosis. PANoptosis is a collective term for programmed cell death (PCD) modalities that encompass elements of apoptosis, pyroptosis, and necroptosis. The accumulation of Aβ peptides and tau proteins, along with the immune response in brain cells, may trigger PANoptosis, thus advancing the progression of the disease. Recent advancements in molecular imaging and genetics have provided deeper insights into the interactions between Aβ peptides, tau proteins, and the immune response. The review also discusses the role of mitochondrial dysregulation in AD. The exploration of the interplay between neurodegeneration, immune responses, and cell death offers promising avenues for the development of innovative treatments.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"2"},"PeriodicalIF":3.3,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922309","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":"Differential Expression of GABA Receptor-Related Genes in Alzheimer's Disease and the Positive Regulatory Role of Aerobic Exercise-From Genetic Screening to D-gal-induced AD-like Pathology Model.","authors":"Yang Liu, Haoran Peng, Qi Liu, Jianying Hao, Chao Tang, Hanhui Yan","doi":"10.1007/s12017-024-08821-1","DOIUrl":"10.1007/s12017-024-08821-1","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common neurodegenerative disorder. The neuropathology of AD appears in the hippocampus. The purpose of this work was to reveal key differentially expressed genes (DEGs) in the hippocampus of AD patients and healthy individuals. Furthermore, we established an in vivo AD-like model to validate and explore the effects of exercise on these risky genes. The datasets GSE36980 and GSE48350 were downloaded from the GEO database and visualized using R packages to obtain DEGs. Subsequently, the potential biological functions of these DEGs were predicted, PPI network interactions were screened for core genes, and Pearson correlation analysis was performed. Additionally, we determined the diagnostic value of core DEGs using ROC curves. Single-cell analysis was used to verify the cell type specificity of hub genes. Finally, we used RT-qPCR, immunohistochemistry, and immunofluorescence to validate the expression of core DEGs in model mice and to explore the beneficial mechanisms of exercise. A total of 13 differentially expressed genes (DEGs) associated with the development of AD were identified, comprising 11 down-regulated genes and 2 up-regulated genes. PPI network visualization acquired four down-regulated core DEGs with good diagnostic value. The findings from the in vivo study indicated that the mRNA expression of GABRA1, GABRG2, and SVOP decreased, and the astrocyte marker GFAP notably increased in AD mice. Surprisingly, exercise increased hippocampal GABRA1 and GABRG2 expression and decreased GFAP-positive intensity of GABRG1 localization, reducing expression of inflammatory markers TNF-α and IL-1β. In addition, exercise improved the spatial exploration ability but had little effect on the preference index in AD mice. Our data highlighted the mechanism by which exercise improves memory performance in AD patients by reducing astrocyte neurotoxicity inducing decreased hippocampal GABA receptor expression.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"1"},"PeriodicalIF":3.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922219","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":"Recent Advances in the miRNA-Mediated Regulation of Neuronal Differentiation and Death.","authors":"Somi Patranabis","doi":"10.1007/s12017-024-08820-2","DOIUrl":"10.1007/s12017-024-08820-2","url":null,"abstract":"<p><p>The review aims to focus on the role of miRNA in gene regulation, related to differentiation and apoptosis of neurons, focusing on the array of miRNAs involved in the processes. miRNAs are a known class of small regulatory RNAs, which in association with RNA processing bodies, play major roles in different cellular events, such as neurogenesis and neuronal differentiation. miRNAs function in controlling neuronal events by targeting different important molecules of cellular signalling. The post-translational modification of Ago2 is crucial in modulating the neurons' miRNA-mediated regulation. Thus, understanding the crosstalk between cellular signalling and miRNA activity affecting neuronal events is very important to decipher novel targets and related signalling pathways, involved in neuronal survival and neurodegeneration.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"52"},"PeriodicalIF":3.3,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795052","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":"Current Status of Research on Nanomaterials Combined with Mesenchymal Stem Cells for the Treatment of Ischemic Stroke.","authors":"Qingxue Xu, Lijuan Gu, Zhiyang Li, Lun Gao, Lu Wei, Zohaib Shafiq, Shigui Chen, Qiang Cai","doi":"10.1007/s12017-024-08819-9","DOIUrl":"10.1007/s12017-024-08819-9","url":null,"abstract":"<p><p>Ischemic stroke (IS) is a disease with high mortality and disability rates worldwide and is a serious threat to patient health. Owing to the narrow therapeutic window, effective treatments during the recovery period are limited. However, in recent years, mesenchymal stem cells (MSCs) have attracted attention and have shown therapeutic potential in IS treatment because of their abilities to home and secrete multiple bioactive substances and potential for differentiation and substitution. The therapeutic mechanisms of MSCs in IS include the regulatory effects of MSCs on microglia, the dual role of MSCs in astrocytes, how MSCs connect innate and adaptive immunity, the secretion of cytokines by MSCs to counteract apoptosis and MSC apoptosis, the promotion of angiogenesis by MSCs to favor the restoration of the blood‒brain barrier (BBB), and the potential function of local neural replacement by MSCs. However, the low graft survival rate, insufficient homing, poor targeting, and inability to achieve directional differentiation of MSCs limit their wide application. As an approach to compensate for the shortcomings of MSCs, scientists have used nanomaterials to assist MSCs in homing, survival and proliferation. In addition, the unique material of nanomaterials adds tracking, imaging and real-time monitoring to stroke treatment. The identification of effective treatments for stroke is urgently needed; thus, an understanding of how MSCs treat stroke and further improvements in the use of nanomaterials are necessary.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"51"},"PeriodicalIF":3.3,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790693","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":"Schizophrenia Biomarkers: Blood Transcriptome Suggests Two Molecular Subtypes.","authors":"Herut Dor, Libi Hertzberg","doi":"10.1007/s12017-024-08817-x","DOIUrl":"10.1007/s12017-024-08817-x","url":null,"abstract":"<p><p>Schizophrenia is a chronic illness that imposes a significant burden on patients, their families, and the health care system. While it has a substantial genetic component, its heterogeneous nature-both genetic and clinical-limits the ability to identify causal genes and mechanisms. In this study, we analyzed the blood transcriptomes of 398 samples (212 patients with schizophrenia and 186 controls) obtained from five public datasets. We demonstrated this heterogeneity by clustering patients with schizophrenia into two molecular subtypes using an unsupervised machine-learning algorithm. We found that the genes most influential in clustering were enriched in pathways related to the ribosome and ubiquitin-proteasomes system, which are known to be associated with schizophrenia. Based on the expression levels of these genes, we developed a logistic regression model capable of predicting schizophrenia samples in unrelated datasets with a positive predictive value of 64% (p value = 0.039). In the future, integrating blood transcriptomics with clinical characteristics may enable the definition of distinct molecular subtypes, leading to a better understanding of schizophrenia pathophysiology and aiding in the development of personalized drugs and treatment options.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"50"},"PeriodicalIF":3.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751416","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":"Transcriptomic Profiling Reveals Sex-Specific Epigenetic Dynamics Involving kdm6b and H3K27 Methylation in Cerebral Ischemia-Induced Neurogenesis and Recovery.","authors":"Mydhili Radhakrishnan, Aditya Undru, Shashikant Patel, Pooja Sharma, Arvind Kumar, Sumana Chakravarty","doi":"10.1007/s12017-024-08816-y","DOIUrl":"10.1007/s12017-024-08816-y","url":null,"abstract":"<p><p>Cerebral ischemic stroke ranks among the leading causes of death and disability worldwide. A significant challenge, beyond the lack of effective therapies, is the frequent oversight of sex as a vital factor in stroke research. This study focuses on elucidating the sex-specific epigenetic mechanisms that contribute to neural damage and recovery in cerebral ischemia. In our previously reported study, we demonstrated that following ischemia-induced cerebral artery occlusion (ICAO), female striatal tissue exhibited an early reinstatement of H3K9me2 marks on the promoters of inflammatory genes compared to male striatal tissue. This restoration led to a reduction in the expression of inflammatory cytokines, ultimately contributing to accelerated recovery in females. Building upon these findings, the current study aimed to investigate the unidentified molecular pathways responsible for the accelerated recovery observed in females. To explore this, we performed illumina-RNA sequencing on striatal tissues 24-h post-ICAO. Interestingly, our analysis revealed differential regulation of H3K27me2 marks on the promoters of various neurogenic genes at an early stage, which facilitated early neurogenesis in the female striatum. This investigation identifies an epigenetic modulator, kdm6b/jmjd3, targeting H3K27, and delineates its sex-specific role in neural stem cell proliferation. The findings contribute to a comprehensive model linking gender-specific epigenetic regulation, neurogenesis, and post-ICAO recovery. In conclusion, the identified epigenetic modulators and their roles in neurogenesis offer potential targets for refined therapeutic interventions, emphasizing the importance of personalized and sex-specific considerations in stroke studies.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"49"},"PeriodicalIF":3.3,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710767","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":"Microparticles Mediate Lipopolysaccharide-induced Inflammation and Chronic Pain in Mouse Model.","authors":"Anjali Singh, Khushi, Vinod Tiwari, Alok Kumar","doi":"10.1007/s12017-024-08809-x","DOIUrl":"10.1007/s12017-024-08809-x","url":null,"abstract":"<p><p>Recent evidence highlights microparticles (MPs) as crucial players in intercellular communication among immune cells, yet their role in inflammation-induced chronic pain remains unexplored. In this study, we investigated the involvement of MPs in the progression of inflammation and associated pain using mouse models of chronic neuroinflammation induced by repeated intraperitoneal injections of lipopolysaccharide (LPS; 1 mg/kg for four consecutive days) in C57BL/6 mice. Chronic pain was analyzed at baseline (day 0) and on day 21 post-LPS injection using von Frey and the hot metal plate tests. We found a significant increase in the levels of proinflammatory mediators and activation of the TLR4-NFκB signaling pathways following LPS administration.  Additionally, transcriptional upregulation of chronic pain-associated TRP channels and glutamate receptors, including TRPA1, TRPM2, and mGluR2 in the cortex and hippocampus as well as mGluR5 in the cortex, was noted on day 21 post-LPS injection. Moreover, upregulation of TRPM2, mGluR2, and mGluR5 was found in the spinal cord, along with increased TRPA1 protein expression in the brain cortex. Plasma-derived MPs were isolated, revealing a significant increase in concentration 21 days after LPS injection, accompanied by TNF-α DNA encapsulation and increased TNF-α mRNA expression within MPs. Furthermore, MPs concentration positively correlated with the expression of TRPA1, TRPM2, mGluR2, and mGluR5. These findings suggest that MPs contribute to inflammation-induced chronic pain, highlighting their potential as therapeutic targets.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"48"},"PeriodicalIF":3.3,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710759","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}