Molecular Neurobiology最新文献

{"title":"Nuclear MicroRNA-124-3p Promotes Neurite Outgrowth After Spinal Cord Injury by Enhancing Cttn Transcription.","authors":"Jin Yang, Junjie Dong, Haotian Li, Zhiqiang Gong, Bing Wang, Kaili Du, Chunqiang Zhang, Lingqiang Chen","doi":"10.1007/s12035-025-04813-9","DOIUrl":"10.1007/s12035-025-04813-9","url":null,"abstract":"<p><p>The outgrowth of motor neurons needs to be enhanced for the efficient recovery of sensory and movement abilities after nerve injury. The microRNA miR-124-3p can repair spinal cord injury (SCI) and promote neurite outgrowth. In this study, we aimed to investigate the effect of miR-124-3p on neurite outgrowth and the mechanism underlying its effect on SCI. Rats with SCI were intrathecally injected with agomiR-124 (miR-124-3p agomiR) for 14 days. The agomiR-124 improved locomotor functions were observed with open-field scoring systems. The levels of miR-124-3p and Cortactin across three weeks, and neuronal biomarkers NF200, Tuj1, Map2 and NeuN post 6 weeks were reduced in rats with SCI, which were reverted with agomiR-124 treatment. The wound scratch assay showed that agomiR-124 enhanced outgrowth of neurites in PC12 cell-derived neuronal like cells. Silencing of Cttn reduced the numbers of neurites and growth cones, while pcDNA-Cttn exerted an opposite effect. The enhanced outgrowth of neurites by agomiR-124 can be reverted by co-treated si-Cttn. Finally, the interactions among miR-124-3p, IPO8, Ago1/2, and the Cttn promoter were verified in PC12 cells through RNA immunoprecipitation, RNA pull-down, and chromatin immunoprecipitation assays. Our results showed that miR-124-3p enhanced the function of neurons and promoted neurite outgrowth following SCI, at least partly by targeting the promoter of Cttn and activating its transcription. These findings elucidated the mechanism underlying the neuroprotective effects of miR-124-3p and revealed the therapeutic ability of the two molecules as targets associated with SCI.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8782-8795"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Potential Protective Effects of Intermittent Fasting Against Radiation-Induced Brain Damage in a Rat Model: Suggested Involvement of IRS-1/PI3 K/AKT and BDNF/TrkB Signaling Pathways.","authors":"Eman F S Taha, Hebatallah E Mohamed, Lobna M Anees, Hayam Mostafa, Eman S Eldin","doi":"10.1007/s12035-025-05059-1","DOIUrl":"https://doi.org/10.1007/s12035-025-05059-1","url":null,"abstract":"<p><p>Fasting has emerged as a promising therapeutic strategy for neurological disorders, offering protection against insults such as ionizing radiation (IR), which can cause irreversible brain damage. Intermittent fasting (IF), including alternate-day fasting (ADF) and time-restricted feeding (TRF), is being explored for its neuroprotective effects with potential involvement of key signaling pathways such as IRS-1/PI3K/AKT and BDNF/TrkB. Thirty-six male Wistar albino rats were randomly divided into six groups: normal feeding (NF, ad libitum feeding), ADF, TRF (6-h feeding window), NF plus radiation (NF-irradiated, 20-Gy cranial exposure), ADF plus radiation (ADF-irradiated), and TRF plus radiation (TRF-irradiated). Oxidative stress markers, antioxidant enzymes, liver and kidney function parameters, and gene/protein expression levels (IRS1, AKT1, PI3K, GFAP, 8-OHdG, BDNF, TrkB) were evaluated using enzyme-linked immunosorbent assay (ELISA) and RT-PCR, complemented by histopathological analysis. IR significantly impaired antioxidant defenses (GSH, GST, CAT), suppressed IRS-1/PI3K/AKT and BDNF/TrkB signaling, and elevated oxidative damage markers (MDA, ROS, 8-OHdG), inflammation (GFAP), and markers of organ dysfunction (ALT, AST, GGT, urea, creatinine). Both IF regimens mitigated these effects; however, TRF demonstrated greater efficacy than ADF. TRF more effectively reduced oxidative stress, improved antioxidant enzyme activity, and more robustly restored metabolic and neurotrophic signaling pathways. Both ADF and TRF provided neuroprotection against radiation-induced brain injury, but TRF exhibited superior outcomes in reducing oxidative stress and preserving neuronal integrity. These findings highlight TRF as a potentially more effective dietary strategy for mitigating radiation-induced neurotoxicity, with possible contributions from the modulation of IRS-1/PI3K/AKT and BDNF/TrkB pathways.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-Analyses of Samples From Amyotrophic Lateral Sclerosis Patients and Controls Identify Many Novel Small RNAs With Diagnostic And Prognostic Potential.","authors":"Phillipe Loher, Eric Londin, Hristelina Ilieva, Piera Pasinelli, Isidore Rigoutsos","doi":"10.1007/s12035-025-04747-2","DOIUrl":"10.1007/s12035-025-04747-2","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous disease for which accurate diagnostic and prognostic biomarkers are needed. Toward this goal, we reanalyzed two published collections of datasets generated from the plasma and serum of ALS patients and controls. We profiled these datasets for isoforms of microRNAs (miRNAs) known as isomiRs, transfer RNA-derived fragments (tRFs), and ribosomal RNA-derived fragments (rRFs), placing all remaining reads into a group labeled \"not-itrs.\" We found that plasma and serum are rich in isomiRs (canonical, non-canonical, and non-templated), tRFs, rRFs, and members of an emerging class of small RNAs known as Y RNA-derived fragments (yRFs). In both analyzed collections, we found many isomiRs, tRFs, rRFs, and yRFs that are differentially abundant between patients and controls. We also performed a survival analysis that considered Riluzole treatment status, demographics (age at onset, age at enrollment, sex), and disease characteristics (ALSFRS, rD50, onset type) and found many of the differentially abundant small RNAs to be associated with survival time, with some of these associations being independent of Riluzole treatment. Unexpectedly, many not-itrs that did not map to the human genome mapped exactly to sequences from the SILVA database of ribosomal DNAs (rDNAs). Not-itrs from the plasma datasets mapped primarily to rDNAs from the order of Burkholderiales, and several of them were associated with patient survival. Not-itrs from the serum datasets also showed support for rDNA from Burkholderiales but a stronger support for rDNAs from the fungi group of the Nucletmycea taxon. The findings suggest that many previously unexplored small non-coding RNAs, including human isomiRs, tRFs, rRFs, and yRFs, could potentially serve as novel diagnostic and prognostic biomarkers for ALS.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8135-8149"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Validation of Biomarkers for Alzheimer's Disease Based on Akt and Wnt Signaling Pathways in Mouse Models.","authors":"Ya-Han Wang, Hong-Yun Wu, Chao Xin, Kai-Xin Zhang, Ji-Wei Zhang, Hong-Wei Zhi","doi":"10.1007/s12035-025-04785-w","DOIUrl":"10.1007/s12035-025-04785-w","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disease that remains challenging to treat. Akt and Wnt play a role in complex cellular signaling, which is crucial for examining the onset of AD. In this study, we aimed to identify and analyze Akt pathway-related genes (ARGs) and Wnt pathway-related genes (WRGs) as AD biomarkers, determine the effects of ARGs and WRGs on AD, and verify these effects in AD mouse models. We searched for differentially expressed genes in the Gene Expression Omnibus database, constructed candidate gene protein-protein interaction networks, and used least absolute shrinkage and selection operator regression analysis and the support vector machine-recursive feature elimination algorithm to screen key genes. Correlation and functional similarity analyses of key genes, immune infiltration analysis, competing endogenous RNA network construction, and drug prediction of key genes were performed. Expression of key genes in streptozotocin-treated (STZ)-treated AD mice was validated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Bioinformatics analysis identified five key genes in AD: PRKACA, CDH3, ATP6V0C, DLL1, and CELSR2. Step-down tests, immunohistochemistry, and silver plate staining confirmed successful treatment of STZ-induced AD in mice. According to RT-qPCR analysis, the relative expression of DLL1 mRNA in AD mice was higher than that in control mice, whereas the relative expression of ATP6V0C and PRKACA mRNA in AD mice was lower than that in control mice; this was consistent with the results of bioinformatics analysis (p < 0.05). This study screened and validated AD biomarkers associated with the Akt and Wnt pathways in mouse models.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8279-8297"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker Profile in Peripheral Blood Cells Related to Alzheimer's Disease.","authors":"Mirko Lomi, Filippo Geraci, Cristina Del Seppia, Cristina Dolciotti, Renata Del Carratore, Paolo Bongioanni","doi":"10.1007/s12035-025-04767-y","DOIUrl":"10.1007/s12035-025-04767-y","url":null,"abstract":"<p><p>In a healthy brain, neuroinflammation, controlled by the main intermediary for the immune response microglia and astrocytes, contributes to maintain physiological functions such as secretion of neurotrophic factors, removal of cell tau and amyloid-β (Aβ) debris, and local homeostasis. When the immune response becomes chronic, it can become pathological and fuel neuroinflammation, causing glial cells to malfunction and not perform their function of clearing debris, resulting in further damage to neurons. Multiple studies highlight that an intense crosstalk is activated between peripheral blood white cells (PBWCs) and central nervous system (CNS). Nevertheless, how PBWC can be carriers of biomarkers of the CNS neuropathological states it is still far to be completely known. In this work, we aimed to observe how PBWC content could be related to moderate-severity of DAT in order to have early signals from of pathological neurodegeneration brain initiate. Protein analysis have been performed in PBWC of Mild Cognitive Impairment (MCI) and DAT patients in respect to those of healthy controls and differently expressed proteins have been investigated. Our data showed a deregulation of pathways involved in neurodegeneration since from MCI level and deregulated proteins that can be considered markers for DAT onset and progression.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8949-8964"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biology, Pathology, and Targeted Therapy of Exosomal Cargoes in Parkinson's Disease: Advances and Challenges.","authors":"Faezeh Almasi, Faeze Abbasloo, Narges Soltani, Masoud Dehbozorgi, Atousa Moghadam Fard, Arash Kiani, Nasim Ghasemzadeh, Hassan Mesgari, Elaheh Zadeh Hosseingholi, Zahra Payandeh, Parjin Rahmanpour","doi":"10.1007/s12035-025-04788-7","DOIUrl":"10.1007/s12035-025-04788-7","url":null,"abstract":"<p><p>Parkinson's disease (PD) involves the loss of dopamine neurons and accumulation of alpha-synuclein (α-syn), leading to Lewy bodies. While α-syn-targeting immunotherapies show promise, clinical application is challenging. Emerging strategies include nano-platforms for targeted delivery and imaging, and cell-based therapies with patient-specific dopaminergic neurons, aiming to enhance treatment effectiveness despite challenges. Exosome-based methodologies are emerging as a promising area of research in PD due to their role in the spread of α-syn pathology. Exosomes are small extracellular vesicles that can carry misfolded α-syn and transfer it between cells, contributing to the progression of PD. They can be isolated from biological fluids such as blood and cerebrospinal fluid, making them valuable biomarkers for the disease. Additionally, engineering exosomes to deliver therapeutic agents, including small molecules, RNA, or proteins, offers a novel approach for targeted therapy, capitalizing on their natural ability to cross the blood-brain barrier (BBB). Ongoing studies are evaluating the safety and efficacy of these engineered exosomes in clinical settings. This review explores the role of exosomes in PD, focusing on their potential for diagnosis, treatment, and understanding of pathology. It highlights advancements and future directions in using exosomes as biomarkers and therapeutic tools.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8381-8399"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Puerarin Alleviates Cerebral Ischemia-Reperfusion Injury by Inhibiting Ferroptosis Through SLC7A11/GPX4/ACSL4 Axis and Alleviate Pyroptosis Through Caspase-1/GSDMD Axis.","authors":"Ying Huang, Jiehong Yang, Ting Lu, Chongyu Shao, Haitong Wan","doi":"10.1007/s12035-025-04798-5","DOIUrl":"10.1007/s12035-025-04798-5","url":null,"abstract":"<p><p>Cerebral ischemia-reperfusion (CIRI) represents a complex disease entity that encompasses multiple pathways. The occurrence of CIRI induces cerebral infarction, accompanied by brain tissue necrosis and focal neuronal impairment. Previous studies have demonstrated that ferroptosis, a specific cell death pathway implicated in CIRI, plays a crucial role in mediating the pathophysiological process of this condition. Puerarin, is known to possess vasodilatory, antioxidant, and neuroprotective properties. However, its precise role in ferroptosis as well as the underlying mechanisms remains elusive. In this study, we delved into the neuroprotective mechanisms of puerarin using both the rat middle cerebral artery occlusion (MCAO) model and the HT22 cell model of oxygen-glucose deprivation/reperfusion (OGD/R). In the MCAO model, puerarin was found to exhibit an inhibitory effect on ACSL4, which was consistent with that of rosiglitazone. Simultaneously, it was capable of counteracting the inhibition of GPX4 by RSL3. These findings suggest that puerarin modulates GPX4 and ACSL4, thereby exerting an inhibitory effect on ferroptosis. The ferroptosis-protective effect of puerarin was further corroborated in the OGD/R through a positive control experiment with ferrostatin-1, a lipid peroxidation inhibitor. Furthermore, we also recognized the importance of other cell death modalities, such as pyroptosis. Consequently, we verified the neuroprotective effect of puerarin by examining the influence of caspase-1 and GSDMD in HT22. Mechanistically, puerarin alleviates CIRI by respectively inhibiting ferroptosis through the SLC7A11/GPX4/ACSL4 axis and pyroptosis through the caspase-1/GSDMD axis. This research provides novel insights into the targeting and therapeutic potential of puerarin for the treatment of CIRI.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8931-8948"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement in the Cognitive Function in Chronic Pain: Therapeutic Potential of the Endocannabinoid System.","authors":"Saeideh Karimi-Haghighi, Maryam Shaygan","doi":"10.1007/s12035-025-04814-8","DOIUrl":"10.1007/s12035-025-04814-8","url":null,"abstract":"<p><p>Chronic pain presents as a complex condition encompassing sensory (Zhang Z et al. Cell Rep 12;752-759, 2015) and emotional components, often accompanied by anxiety, depression, insomnia, and cognitive impairment. These factors significantly hinder daily activities and rehabilitation efforts. The widespread prevalence of chronic pain imposes substantial clinical, societal, and economic burdens. While current analgesics have limitations and associated side effects such as tolerance, dependency, cognitive deficits, and a narrow therapeutic window, the search for new analgesic options remains imperative. The endocannabinoid system (ECS), a key modulator in pain processing pathways, plays a crucial role in executive functions. This review specifically focuses on the cognitive impairments associated with chronic pain and highlights the pivotal role of the ECS in the cognitive aspects of pain. Additionally, the effectiveness of cannabinoid-based medications in improving executive functions in patients with chronic pain is evaluated.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"8977-8985"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Clinic to Mechanisms: Multi-Omics Provide New Insights into Cerebrospinal Fluid Metabolites and the Spectrum of Psychiatric Disorders.","authors":"Jie Wen, Yingjie Li, Yu Chen, Yongzhen Li, Bin Yu, Hongwei Liu, Zhiwei Xia, Jingwei Zhang","doi":"10.1007/s12035-025-04773-0","DOIUrl":"10.1007/s12035-025-04773-0","url":null,"abstract":"<p><p>Cerebrospinal fluid (CSF) is crucial in maintaining brain homeostasis by facilitating waste clearance, nutrient transport, and immune signaling. However, the links between CSF metabolites and psychiatric disorders, as well as the underlying mechanisms, remain largely unexamined. We conducted a bidirectional two-sample Mendelian randomization analysis to investigate potential causal relationships between CSF metabolites and 12 psychiatric disorders. Summary data for psychiatric disorders were sourced from the Psychiatric Genomics Consortium, while information on CSF metabolites was derived from two studies within the Wisconsin Alzheimer's Disease cohort. Causal estimates and pleiotropy were assessed using several robust methods, including inverse-variance-weighted (IVW) analysis, weighted median analysis, MR-Egger regression, and the MR-Egger test. Furthermore, a transcriptome-wide association study was conducted to explore potential mechanisms and shared etiologies between CSF metabolites and psychiatric disorders. The genetic risk of eating disorders (ED) can be increased by leucine (OR = 1.55, 95% CI: 1.21-1.97, P = 4.35 × 10⁻⁴), salicylate (OR = 1.03, 95% CI: 1.01-1.04, P = 4.95 × 10⁻⁴), and 1-methylnicotinamide (OR = 1.06, 95% CI: 1.03-1.09, P = 6.94 × 10⁻⁶), while methylmalonate may reduce ED risk (OR = 0.95, 95% CI: 0.93-0.98, P = 1.31 × 10⁻⁴). Similarly, the risk of schizophrenia (SCZ) may be reduced by threonate (OR = 0.93, 95% CI: 0.89-0.97, P = 1.98 × 10⁻⁴), oxalate (OR = 0.94, 95% CI: 0.90-0.97, P = 3.15 × 10⁻⁴), phenyllactate (OR = 0.96, 95% CI: 0.94-0.98, P = 2.23 × 10⁻⁴), N-acetylglucosamine (OR = 0.98, 95% CI: 0.97-0.99, P = 3.57 × 10⁻⁵), and citramalate (OR = 0.98, 95% CI: 0.98-0.99, P = 5.78 × 10⁻⁴). Conversely, SCZ may upregulate gamma-glutamylleucine (β = 0.08, P = 1.97 × 10⁻⁴) and O-sulfo-L-tyrosine (β = 0.06, P = 1.25 × 10⁻⁴), while downregulating gamma-glutamylphenylalanine (β = - 0.50, P = 1.16 × 10⁻⁴). Signal pathways related to the mechanistic target of the rapamycin (mTOR), post-translational protein modifications, and immune regulation may mediate the causal relationship of CSF metabolites on ED and SCZ. We identified a casual genetic causal relationship between CSF metabolites and both ED and schizophrenia SCZ, which is potentially mediated by pathways related to energy metabolism, post-translational modifications, and immune regulation.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"9120-9132"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating Causal Links Between Gut Microbiota and Neurological Disorders via Genome-Wide Association Studies.","authors":"Qingchen Jiang, Laiqiang Wu, Xiaochen Wang, Zhe Gao, Xiaorui Liu, Wen Zhang, Li Xue, Juan Yang, Teng Chen, Yanjiong Chen, Biao Wang","doi":"10.1007/s12035-025-04770-3","DOIUrl":"10.1007/s12035-025-04770-3","url":null,"abstract":"<p><p>Many reports have highlighted the involvement of the gut microbiome in the occurrence, progression, and outcomes of neurological disorders. However, current reports are somewhat chaotic, especially concerning whether the gut microbiota has a causal effect on various neurological diseases. Furthermore, whether there is a common mechanism involving gut microbial communities in these neurological disorders has not to be revealed. In this study, we leveraged data from the largest-scale genome-wide association study (GWAS) by the MiBioGen consortium, which includes genetic and microbial composition data from 18,340 individuals spanning 24 cohorts. We utilized single-nucleotide polymorphisms (SNPs) associated with the gut microbiome as instrumental variables (IVs) in Mendelian randomization (MR) analyses. These IVs were rigorously selected based on their genome-wide and locus-wide significance to ensure robust causal inference. Our study established robust associations between specific gut microbiota and various neurological disorders using MR. We systematically depicted the bacteria with causal relationships in all diseases, covering the levels of phylum, class, order, family, and genus. We identified 34 bacterial species as significant risk or protective factors across disorders, including two main phylum levels such as Firmicutes (22 species) and Proteobacteria (8 species), as well as Bacteroidetes (2 species), Actinobacteria (1 species), and Verrucomicrobiota (1 species). At the family level of bacteria, we found that Lachnospiraceae and Ruminococcaceae are the most related to these 11 diseases and they may play different roles in the same disease.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"9000-9017"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}