Journal of Molecular Neuroscience最新文献

{"title":"Effects of Pharmacological Treatment on Telomere Length and the Expression of Telomerase/Shelterin-Related Genes in Rat Models of Autism","authors":"Elena V. Valeeva,&nbsp;Dmitry O. Nikitin,&nbsp;Lubov S. Nikiforova,&nbsp;Irina I. Semina,&nbsp;Ildus I. Ahmetov","doi":"10.1007/s12031-025-02353-4","DOIUrl":"10.1007/s12031-025-02353-4","url":null,"abstract":"<div><p>Telomeres are increasingly recognized for their potential role in the etiology of autism spectrum disorder (ASD) due to their involvement in cellular aging and telomerase-shelterin function. Although shorter telomeres have been observed in individuals with ASD, studies linking telomere dynamics in blood cells and brain regions remain limited. Using the valproic acid (VPA, 500 mg/kg) rodent model, this study aimed to assess the impact of three drugs commonly used in ASD treatment (amitriptyline, risperidone, and nooclerin) on telomere length and the expression of telomerase/shelterin-related genes (<i>Dkc1</i>, <i>Gar1</i>, <i>Pot1a</i>, <i>Pot1b</i>, <i>Tep1</i>, <i>Terc</i>, <i>Terf2ip</i>, <i>Tert</i>, <i>Tinf2</i>, <i>Tnks</i>, <i>Tpp1</i>, <i>Trf1</i>, and <i>Trf2</i>) in blood cells, the prefrontal cortex, and hippocampus of VPA-exposed Wistar rats. Telomere length and gene expression were measured using quantitative PCR. Risperidone treatment in VPA males resulted in telomere elongation and increased expression of <i>Tnks</i> in blood cell and <i>Trf1</i>, <i>Trf2</i> genes in prefrontal cortex. Nooclerin treatment also showed beneficial effects on telomere length of blood cell in males, alongside increased <i>Trf1</i> expression. Long telomeres in male blood cells were associated with reduced anxiety, while a positive correlation was found between <i>Tpp1</i> expression and stereotypical behavior in both male and female VPA rats. These findings suggest that nooclerin and risperidone influence telomere length and gene expression related to the telomere-telomerase complex in a sex-dependent manner, offering insights into the neurobiological mechanisms underlying ASD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-025-02353-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871171","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":"SERPINH1 and CTSZ are Key Markers of Glioma Angiogenesis","authors":"Haotian Wei,&nbsp;Xinlong Li,&nbsp;Peng Feng,&nbsp;Zhaohui He","doi":"10.1007/s12031-025-02349-0","DOIUrl":"10.1007/s12031-025-02349-0","url":null,"abstract":"<div><p>Glioma, as one of the most complex and prognostically variable malignant tumors of the central nervous system, poses a significant challenge to clinical decision-making due to its molecular heterogeneity. This study aims to deepen our understanding of glioma molecular subtypes and explore key gene markers with prognostic and diagnostic value. We utilized an angiogenesis-related gene set and employed the Non-negative Matrix Factorization (NMF) algorithm to successfully identify two distinct prognostic subtypes, with subtype one exhibiting more unfavorable prognostic characteristics. To further elucidate the biological functional differences between these two subtypes, we conducted Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA). Building on this, we integrated differentially expressed genes between subtypes with core genes revealed by Weighted Gene Co-expression Network Analysis (WGCNA) through intersection analysis to pinpoint a series of key candidate genes. Subsequently, we constructed a Protein–Protein Interaction (PPI) network to identify genes occupying central nodes within the network. To screen markers with high specificity and sensitivity for prognosis and diagnosis, we adopted a dual-track strategy: on the one hand, we utilized machine learning algorithms such as Lasso regression, Support Vector Machine (SVM), and Random Forest (RF) to select core genes, identifying markers that can accurately predict the subtype with a poor prognosis; on the other hand, we employed a comprehensive evaluation system incorporating 101 machine learning ensemble algorithms to further validate and screen prognosis-related genes. Through cross-validation using these two strategies, we ultimately determined SERPINH1 and CTSZ as dual prognostic and diagnostic markers for glioma. This study not only provides a new perspective and tool for the molecular subclassification of glioma but also, through a rigorous multi-algorithm, multi-dimensional screening process, uncovers SERPINH1 and CTSZ as markers with potential clinical translational value. These findings are expected to offer more precise biomarker support for the early diagnosis and prognostic assessment of glioma, potentially paving new avenues for the development of personalized treatment strategies and improving patient outcomes. This has far-reaching implications for the clinical management of glioma in the field of neurosurgery.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852510","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":"Metabolic Reprogramming in Spinal Cord Injury and Analysis of Potential Therapeutic Targets","authors":"Xiangjun Chen,&nbsp;Juan Wang,&nbsp;Peiran Chan,&nbsp;Qian Zhu,&nbsp;Ziyan Zhu,&nbsp;Mingming Zheng,&nbsp;Xinyi Chen,&nbsp;Haozhen Wu,&nbsp;Min Cui,&nbsp;Yongjie Zhang","doi":"10.1007/s12031-025-02343-6","DOIUrl":"10.1007/s12031-025-02343-6","url":null,"abstract":"<div><p>Spinal cord injury (SCI) is a critical neurological disorder that frequently leads to permanent disability, profoundly affecting the quality of life of individuals with SCI. In this research, we examined the varied expression of genes associated with metabolic reprogramming–related genes in SCI. By employing the Gene Expression Omnibus datasets GSE5296 and GSE47681, 1001 differentially expressed genes (DEGs) were identified through the limma R package. Among these, 871 and 130 genes were upregulated and downregulated, respectively. A subset of 10 metabolic reprogramming–related differentially expressed genes (MRRDEGs) was recognized as key players in metabolic reprogramming. Analyses of enrichment performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes indicated that the identified MRRDEGs predominantly participated in processes related to pyruvate metabolism and carbohydrate degradation. Nine hub genes were discerned using a protein–protein interaction network. Subsequently, an SCI mouse model was established using the LISA SCI modeling device, and preliminary validation was conducted through quantitative real-time PCR experiments at various time points after SCI, specifically on days 1, 3, and 7, suggesting their central role in SCI. Receiver operating characteristic curve analysis indicated that these MRRDEGs could be used to diagnose SCI. The CIBERSORT algorithm analysis of immune infiltration identified an inverse relationship between M0 and M2 macrophages. Furthermore, a positive relationship was observed between <i>Ucp2</i> and M0 macrophages, underscoring their essential function in the immune response following SCI. These results highlight MRRDEGs’ importance in SCI and propose their potential roles as targets for therapeutic interventions.</p><h3>Graphical Abstract</h3><p>Using data from the public GEO database, we identified differentially expressed genes associated with metabolic reprogramming in spinal cord injury and successfully validated them through qPCR experiments.</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840351","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":"Identification of Recurrence-associated Gene Signatures and Machine Learning-based Prediction in IDH-Wildtype Histological Glioblastoma","authors":"Min Yuan,&nbsp;Xueqin Hu,&nbsp;Zeng Yang,&nbsp;Jingsheng Cheng,&nbsp;Haibin Leng,&nbsp;Zhiwei Zhou","doi":"10.1007/s12031-025-02345-4","DOIUrl":"10.1007/s12031-025-02345-4","url":null,"abstract":"<div><p>Glioblastoma (GBM) is a highly aggressive brain tumor with frequent recurrence, yet the molecular mechanisms driving recurrence remain poorly understood. Identifying recurrence-associated genes may improve prognosis and treatment strategies. We applied weighted gene co-expression network analysis (WGCNA) to transcriptomic data from IDH-wildtype histological GBM in the CGGA-693 (n = 190) and CGGA-325 (n = 111) cohorts to identify recurrence-associated genes. These genes were validated using RT-qPCR and single-cell RNA sequencing (scRNA-seq) datasets (GSE174554, GSE131928). Their associations with immune cell composition were analyzed. Finally, we evaluated 113 machine learning algorithms to develop a multi-gene predictive model for GBM recurrence, with model performance assessed using receiver operating characteristic (ROC) curves and confusion matrix analysis. We identified eight recurrence-associated genes (<i>CERS2, EML2, FNBP1, ICOSLG, MFAP3L, NPC1, ROGDI, SLAIN1</i>) that were significantly differentially expressed between primary and recurrent GBM. The scRNA-seq analysis revealed cell-type-specific expression patterns, with eight genes predominantly enriched in oligodendrocytes, malignant GBM subtypes, and immune cells. Immune cell deconvolution showed significant alterations in macrophage polarization and NK cell activation in recurrent GBM. Machine learning analysis demonstrated that random forest (RF) was the most effective model, achieving AUC values of 0.998, 0.968, and 0.998 in the training, CGGA-693 validation, and CGGA-325 validation cohorts, respectively, suggesting high predictive accuracy. This study identifies novel recurrence-associated molecular signatures and establishes a machine learning-based predictive model in IDH-wildtype histological GBM.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830870","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":"lncRNA PAN3-AS1 Modulates Cilium Assemble Signaling Pathway Through Regulation of RPGR as a Potential MS Diagnostic Biomarker: Integrated Systems Biology Investigation","authors":"Yasaman Mostaghimi,&nbsp;Mohammad Haddadi,&nbsp;Zohreh Hojjati","doi":"10.1007/s12031-025-02331-w","DOIUrl":"10.1007/s12031-025-02331-w","url":null,"abstract":"<div><p>Multiple sclerosis (MS), an autoimmune condition of the central nervous system (CNS), can lead to demyelination and axonal degeneration in the brain and spinal cord, which can cause progressive neurologic disability. MS symptoms include dysautonomia and progressive decline in motor abilities. In this investigation, we performed an integrated bioinformatics and experimental approach to find the expression level and interaction of a novel long non-coding RNA (lncRNA), <i>PAN3-AS1</i>, in MS samples. Microarray analysis was performed by R Studio using GEOquery and limma packages. lncRNA-mRNA RNA interaction analysis was performed using the lncRRIsearch database. Pathway enrichment analysis was performed by KEGG and Reactome online software through the Enrichr database. Protein–protein interaction analysis was performed by STRING online software. Gene ontology (GO) analysis was performed by Enrichr database. Based on microarray analysis, lncRNA <i>PAN3-AS1</i> has a significantly low expression in MS samples compared to the control (logFC − 1.2, adj. <i>P</i>. Val 0.03). qRT-PCR results approved bioinformatics analyses. ROC analysis revealed that <i>PAN3-AS1</i> could be considered a potential diagnostic biomarker of MS. Based on lncRNA-mRNA interaction analysis, lncRNA <i>PAN3-AS1</i> regulates the expression level of RPGR. RPGR and its protein interactome regulate the cilium assembly, chaperon-mediated autophagy, and microarray biogenesis. lncRNA <i>PAN3-AS1</i>, as a significant low-expressed lncRNA in MS samples, could be a potential diagnostic MS biomarker. <i>PAN3-AS1</i> might regulate the expression level of cilium assembly and chaperon-mediated autophagy. Dysregulation of <i>PAN3-AS1</i> might affect the expression of RPGR and its protein interactome.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830869","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 tRNA Fragments on Neurogenesis Alteration by H₂O₂-induced Oxidative Stress","authors":"Bilge Karacicek,&nbsp;Esra Katkat,&nbsp;Leman Binokay,&nbsp;Gunes Ozhan,&nbsp;Gökhan Karakülah,&nbsp;Sermin Genc","doi":"10.1007/s12031-025-02330-x","DOIUrl":"10.1007/s12031-025-02330-x","url":null,"abstract":"<div><p>Transfer RNAs (tRNAs) are small non-coding RNA molecules transcribed from tRNA genes. tRNAs cleaved into a diverse population tRNA fragments (tRFs) ranging in length from 18 to 40 nucleotides, they interact with RNA binding proteins and influence the stability and translation. Stress is one of the reasons for tRFs cleavage. In our study, we modeled oxidative stress conditions with hydrogen peroxide (H₂O₂) exposure and dealt with one of the frequently expressed tRF in the hippocampus region of the brain, which is tRF-Glu-CTC. For this purpose, neural stem cells (NSCs) were exposed to H₂O₂, and tRF-Glu-CTC levels were increased in various H₂O₂ concentrations. A decrease was seen in microtubule-associated protein 2 (MAP2) marker expression. To understand the H₂O₂ oxidative stress condition on the expression of tRNA fragments, 72 hpf zebrafish embryos exposed to different H₂O₂ concentrations, an increase in the level of tRF-Glu-CTC was observed in all concentrations of H₂O₂ compared to control. Subsequently, neurogenesis markers were figured out via Calb2a (calbindin 2a) in situ hybridization (ISH) and HuC/D immunofluorescence staining (IF) staining experiments. Under H₂O₂ exposure, a decline was observed in Calb2a and HuC/D markers. To understand the inhibitory role of tRF-Glu-CTC on neurogenesis, NSCs were transfected via tRF-Glu-CTC inhibitor, and neurogenesis markers (ßIII-tubulin, MAP2, and GFAP) were determined with qRT-PCR and IF staining. tRF-Glu-CTC inhibitor reversed the diminished neuronal markers expression under the exposure of H₂O₂. Gene Ontology (GO) enrichment analysis showed us that targets of tRF-Glu-CTC are generally related to neuronal function and synaptic processes.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-025-02330-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821951","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":"Fucoxanthinol Mitigates the Cytotoxic Effect of Chlorpyrifos and MPTP on the Dopaminergic Differentiation of SH-SY5Y Human Neuroblastoma Cells","authors":"Ekramy M. Elmorsy,&nbsp;Ayat B. Al-Ghafari,&nbsp;Huda A. Al Doghaither,&nbsp;Mona M. Elghareeb,&nbsp;Mouhamed Alsaqati","doi":"10.1007/s12031-025-02342-7","DOIUrl":"10.1007/s12031-025-02342-7","url":null,"abstract":"<div><p>This study investigates the neuroprotective effects of fucoxanthinol (FXL) against the toxic activities of two compounds known to induce neurotoxic effects in humans and animals. MPTP (1-methyl- 4-phenyl- 1,2,3,6-tetrahydropyridine) induces Parkinson’s disease (PD)-like phenotypes by inhibiting mitochondrial complex I in dopaminergic neurons. Chlorpyrifos (CPF), another neurotoxic agent, is associated with acute and long-term neurotoxicity primarily through acetylcholinesterase (AChE) inhibition. FXL demonstrated the ability to reverse the neurotoxic effects of CPF and MPTP in SH-SY5Y dopaminergic neuronal cell models. Treatment with FXL enhances mitochondrial function in SH-SY5Y cells exposed to CPF and MPTP, as demonstrated by increased levels of Adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), mitochondrial complexes activities, and oxygen consumption rates, pyruvate dehydrogenase (PDH) activities, and mitophagy pathways. This improvement highlights FXL’s ability to counteract the mitochondrial dysfunction induced by these neurotoxic agents. Additionally, FXL reduces oxidative damage and enhances cell viability. At the molecular level, the neuroprotective effects were also associated with the modulation of apoptotic cell markers, including Bcl- 2 and the oxidative damage markers. Molecular docking data further support the outcomes of our in vitro studies. Multivariable analysis highlights the neuroprotective effects of FXL. These findings indicate the potential of FXL to mitigate CPF- and MPTP-induced neurotoxicity, suggesting its promise as a therapeutic agent for managing neuronal damage observe in PD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-025-02342-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801141","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":"FMRP Controls Neuronal Architecture and Synaptic Content of NMDA Receptors in Cultured Hippocampal Neurons","authors":"Elisa Corti,&nbsp;Carlos B. Duarte","doi":"10.1007/s12031-025-02325-8","DOIUrl":"10.1007/s12031-025-02325-8","url":null,"abstract":"<div><p>Fragile X syndrome is the most common inherited form of intellectual disability and is caused by the transcriptional silencing of the <i>Fmr1</i> gene and the lack of fragile X messenger ribonucleoprotein (FMRP). FMRP is an RNA-binding protein that regulates the synthesis of synaptic proteins which are essential for proper brain function. Although circuit hyperexcitability is a hallmark of fragile X syndrome (FXS), the cell-autonomous effects of FMRP deficiency remain poorly understood. In this work, we investigated the functional consequences of the absence of FMRP on neuronal morphology and on ionotropic glutamate receptor surface distribution, using primary cultures of mice hippocampal neurons isolated from wild-type (WT) and <i>Fmr1</i> knock-out (KO) pups. MAP2 staining of <i>Fmr1</i> KO neurons showed a decrease in total dendritic length and complexity of the dendritic tree, accompanied by an increase in soma size compared to WT neurons. Moreover, immunolabelling of surface glutamate receptors performed under non-permeabilising conditions showed that <i>Fmr1</i> KO neurons presented a higher content of synaptic surface GluN2A and a lower content of GluN2B subunits of NMDA receptors, while GluA1 and GluA2 distribution remained unchanged. Finally, multielectrode array data showed that <i>Fmr1</i> KO neurons presented reduced spontaneous activity compared to control neurons. These data support the hypothesis that at the cellular level, <i>Fmr1</i> KO hippocampal neurons are less excitable due to altered input processing, driven by structural defects and altered GluN2A expression in the synaptic plasma membrane.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-025-02325-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749227","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":"The Role of a Novel TRIP12 Mutation in Intellectual Disability: A Molecular and Clinical Investigation in Multiplex Family","authors":"Ramiz Nobakht,&nbsp;Sara Arish,&nbsp;Shirin Hasanzadeh,&nbsp;Haleh Mokabber,&nbsp;Sana davarnia,&nbsp;Hourieh Kalhor,&nbsp;Behzad Davarnia","doi":"10.1007/s12031-025-02336-5","DOIUrl":"10.1007/s12031-025-02336-5","url":null,"abstract":"<div><p>Thyroid hormone receptor interactor 12 (<i>TRIP12</i>; MIM #617,752) is an autosomal dominant hereditary disorder involved in the ubiquitin fusion degradation pathway and the regulation of DNA damage-induced chromatin ubiquitination. Positioned on chromosome 2 at position 2q36.3, <i>TRIP12</i> is a member of the E3 ubiquitin ligase family. This gene plays a vital role in proteasomal degradation by catalyzing substrate ubiquitination and regulating processes such as cell cycle progression, DNA damage repair, and chromatin remodeling. Mutations in <i>TRIP12</i> can result in intellectual disability (ID), Clark-Baraitser syndrome, and various physical and behavioral abnormalities. The proband, a 32-year-old male, exhibited intellectual disability, delayed speech, and behavioral abnormalities without autistic spectrum disorders. The novel <i>TRIP12</i> variant was detected through WES and validated by Sanger sequencing in affected family members. In silico tools predicted the deleterious effect of the variant, and protein modeling indicated significant structural changes. RT-qPCR demonstrated increased <i>TRIP12</i> mRNA levels, suggesting a compensatory mechanism for decreased protein stability. This study examines the role of the TRIP12 gene in the ubiquitin pathway and associated pathologies such as intellectual disability and developmental delay.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761715","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":"Unraveling the Role of LRP1 in Alzheimer’s Disease: A Focus on Aβ Clearance and the Liver-Brain Axis","authors":"Wanyue Yang,&nbsp;Zilin Wei,&nbsp;Tianhui Wang","doi":"10.1007/s12031-025-02339-2","DOIUrl":"10.1007/s12031-025-02339-2","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is the most prevalent form of dementia, significantly contributing to the global health burden. The progressive accumulation of amyloid-beta (Aβ) plaques and tau tangles triggers neuroinflammation, oxidative stress, and neuronal damage, highlighting the critical need for effective clearance mechanisms. Recent research has identified low-density lipoprotein receptor-related protein 1 (LRP1) as a key factor in the regulation of Aβ clearance, neuroinflammation, and blood–brain barrier integrity, particularly in relation to the liver-brain axis. This review provides a comprehensive examination of the role of LRP1 in AD, focusing on its expression in the brain and liver, its contribution to Aβ metabolism, and its potential as a therapeutic target. Using a systematic literature review, LRP1’s multifaceted roles across various biological processes were explored, including its involvement in Aβ transport, clearance via the liver, and modulation of neuroinflammation. Additionally, the impact of physical exercise, pharmacological interventions, and dietary factors on LRP1 expression levels was investigated, elucidating how these approaches may enhance Aβ clearance. The findings demonstrate that LRP1 expression decreases progressively as AD advances, and that augmenting LRP1 activity—particularly through exercise and drug therapies—can improve Aβ clearance and reduce neuroinflammatory responses. Furthermore, LRP1’s involvement in the liver-brain axis reveals its broader systemic role in AD pathology. In conclusion, targeting LRP1 offers a promising avenue for AD prevention and treatment, providing new insights into the therapeutic potential of enhancing Aβ clearance pathways through the liver-brain axis.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143740865","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}