Journal of Molecular Neuroscience最新文献

{"title":"The Role of TRPV4 in Repeated Variate Stress-Induced Increases in Voiding Frequency and Somatic Sensitivity in Male and Female Mice","authors":"Beatrice M. Girard,&nbsp;Lydia Vadnal,&nbsp;Benjamin F. Stebbins McCaffrey,&nbsp;Susan E. Campbell,&nbsp;Margaret A. Vizzard","doi":"10.1007/s12031-026-02547-4","DOIUrl":"10.1007/s12031-026-02547-4","url":null,"abstract":"<div><p>Psychological stress is a known precipitant of lower urinary tract (LUT) dysfunction and can exacerbate pelvic pain, yet the underlying mechanisms remain incompletely understood. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel expressed in LUT tissues and associated afferent circuits, is positioned to couple stress-related signaling to changes in voiding function. We tested the hypothesis that TRPV4 is required for repeated variate stress (RVS)-evoked bladder dysfunction and contributes to stress-associated somatic hypersensitivity and anxiety-like behavior. Male and female wild-type (WT) and <i>Trpv4</i> knockout (KO) mice underwent RVS and were assessed using conscious cystometry, void spot assay (VSA), mechanical sensitivity testing (pelvic and hindpaw), and behavioral assays (open field, elevated plus maze). RVS produced sex- and tissue-specific regulation of <i>Trpv4</i> transcripts LUT tissues. In WT mice, RVS induced bladder overactivity in both sexes, characterized by increased voiding frequency and reduced intermicturition interval. These stress-induced changes were absent in <i>Trpv4</i> KO mice, demonstrating that TRPV4 is required for stress-evoked bladder dysfunction. Bladder pressure endpoints revealed additional sex-dependent effects in WT but not <i>Trpv4</i> KO mice. VSA identified sex-specific spontaneous voiding changes that did not uniformly parallel cystometric measures, indicating complementary sensitivity of provoked and unprovoked assays. Despite protection from stress-associated bladder dysfunction, <i>Trpv4</i> KO mice exhibited increased pelvic and hindpaw mechanical sensitivity following RVS. Behavioral testing revealed sex-dependent differences in stress resilience. These findings identify TRPV4 as a key mediator of stress-induced bladder overactivity and demonstrate a dissociation between referred mechanical pain outcomes in <i>Trpv4</i> KO mice.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13219090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040651","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":"Spinal Cord CELF4 in Chronic Constriction Injury-Induced Neuropathic Pain: Association with TRPV1 and COX-2 Expression","authors":"Guanxiang Kong,&nbsp;Rui Tan,&nbsp;Xianming Zeng,&nbsp;Hailong Zhang,&nbsp;Bin Zhang,&nbsp;Jiasheng Yu,&nbsp;Rushan Xie","doi":"10.1007/s12031-026-02538-5","DOIUrl":"10.1007/s12031-026-02538-5","url":null,"abstract":"<div><p>Despite significant advancements, the mechanisms underlying neuropathic pain remain poorly understood, making it challenging for effective pain management. This study investigated the role of CUGBP Elav-Like Family Member 4 (CELF4), an RNA-binding protein, in modulating pain pathways in neuropathic pain conditions. The results showed a reduction in both mRNA and protein levels of CELF4 in the spinal cord of a chronic constriction injury (CCI) mouse model, suggesting its potential role in response to nerve injury. To further explore the role of CELF4 in modulating pain pathways in vivo, an adeno-associated virus (AAV) was injected into mice to overexpress CELF4. The mice overexpressing CELF4 showed reduced hypersensitivity to mechanical and thermal stimuli as compared to controls, indicating effective mitigation of neuropathic pain symptoms. Mechanistically, the overexpression of CELF4 significantly downregulated the expressions of Transient Receptor Potential Vanilloid-1 (TRPV1) and Cyclooxygenase-2 (COX2), which are crucial mediators of pain signaling. In contrast, the knockdown of CELF4 rescued the TRPV and COX2 expressions, indicating that CELF4 might act as a suppressive regulator in neuropathic pain pathways. These results suggested that CELF4 played a critical role in regulating neuropathic pain by modulating specific ion channels and inflammatory markers, thus offering potential targets for therapeutic intervention in pain management.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13219188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040662","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":"High Mobility Group Box 1 contributes to Neuroinflammation and Central Sensitization After Nitroglycerin Stimulation in Mice","authors":"Ting Long,&nbsp;Shujiang Zhang,&nbsp;Yuan Yang,&nbsp;Ling Li,&nbsp;Xiu Chen","doi":"10.1007/s12031-026-02549-2","DOIUrl":"10.1007/s12031-026-02549-2","url":null,"abstract":"<div><h3>Objective</h3><p>The objective of this research was to clarify the effect of High Mobility Group Box 1 (HMGB1) in chronic migraine (CM).</p><h3>Methods</h3><p>We established a CM model by repeated intraperitoneal injection of nitroglycerin (NTG). Subsequently, Western blot was used to detect changes in HMGB1 protein expression at the trigeminal nucleus caudalis (TNC), and immunofluorescence was performed to determine HMGB1 intracellular localization. After model establishment, HMGB1 inhibitors Glycyrrhizin were administered intraperitoneally for 9 consecutive days. The paw withdrawal threshold (PWT) were measured using the electronic von Frey filament stimulation method. Additionally, changes in phosphorylated-ERK (p-ERK) and inducible nitric oxide synthase (iNOS) expression, as well as calcitonin gene-related peptide (CGRP) release levels at the TNC, were detected by WB and immunofluorescence staining.</p><h3>Results</h3><p>The study revealed a significant increase of HMGB1 starting on day one, which peaked on day nine. Elevated levels remained significantly high for two weeks after NTG administration(<i>p</i> &lt; 0.05). Additionally, HMGB1 was expressed in the nuclei of neurons, microglia and astrocytes. Behavioral assessments indicated a significant reduction in PWT from day five onward, indicative of mechanical hypersensitivity, which was alleviated following treatment with Glycyrrhizin(<i>p</i> &lt; 0.05).The increased expression of p-ERK and iNOS, as well as the elevated levels of CGRP, were all significantly reduced following Glycyrrhizin treatment(<i>p</i> &lt; 0.05).</p><h3>Conclusions</h3><p>These results show that HMGB1 plays a pivotal function in migraine by regulating neuroinflammation and central sensitization. Targeting HMGB1 may be able to mitigating chronic migraine.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040637","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":"N-Glycosylation of mGluR6 Modulates Receptor Cell-Surface Transport, G-Protein Coupling, and Interactions With Synaptic Adhesion Molecules","authors":"Takumi Akagi,&nbsp;Ikuo Ogiwara,&nbsp;Atsushi Shimohata,&nbsp;Ryota Takeda,&nbsp;Tomomi Sakamoto,&nbsp;Daisuke Kato,&nbsp;Makoto Kaneda","doi":"10.1007/s12031-026-02546-5","DOIUrl":"10.1007/s12031-026-02546-5","url":null,"abstract":"<div><p>Metabotropic glutamate receptor 6 (mGluR6) is a synaptic receptor expressed predominantly in retinal ON-bipolar cells. The N-terminal extracellular domain (ECD) of mGluR6 engages in ligand binding and also participates in mGluR6 cell-surface localization and trans-synaptic cell-adhesion complex formation. We herein investigated whether N-glycosylation in the mGluR6 ECD is involved in modulating receptor cell-surface transport, G-protein coupling, and interactions with Elfn1 and Lrit1 using 293T cells expressing ECD mutants with the asparagine-to-glutamine (N-to-Q) substitution in N-glycosylation sequons. The results obtained showed that mGluR6 underwent N-glycosylation at the asparagine residues N290, N445, N473, and N561 in the ECD, and the simultaneous blockage of N-glycosylation at these sites reduced cellular mGluR6 levels. Furthermore, mGluR6 cell-surface levels were decreased by N290Q and N445Q, but unaffected by N473Q and N561Q, while each N-to-Q substitution at the respective sites consistently impaired glutamate-induced G-protein-mediated responses. We also showed that mGluR6 was pulled down with Elfn1 in vitro, and coimmunoprecipitated with Lrit1 in co-transfected cells. The mGluR6-Elfn1 interaction was inhibited by N445Q and facilitated by N473Q and N561Q, whereas the mGluR6-Lrit1 interaction was promoted by N290Q and suppressed by N561Q. Collectively, these results indicate that each of the N-glycosylation sites contributed to efficient G-protein coupling, while the respective sites were involved in the modulation of receptor cell-surface transport and adhesion complex formation with Elfn1 and also with Lrit1 in distinct directions. Therefore, the N-glycosylation of synaptic receptors may have roles in modulating trans-synaptic bridge formation, potentially influencing the tuning of signal transmission.</p><h3>Graphic Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025501","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":"Sex-Related Differences in Circular RNA Expression in Multiple Sclerosis: A Pilot Study","authors":"Valeria Lodde,&nbsp;Ignazio Roberto Zarbo,&nbsp;Gabriele Farina,&nbsp;Enrico Zoroddu,&nbsp;Paolo Solla,&nbsp;Giuseppe Delogu,&nbsp;Myriam Gorospe,&nbsp;Matteo Floris,&nbsp;Ilaria Campesi,&nbsp;Maria Laura Idda","doi":"10.1007/s12031-026-02548-3","DOIUrl":"10.1007/s12031-026-02548-3","url":null,"abstract":"<div><p>Multiple Sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS), with a female-to-male ratio of up to 3:1. Sex differences in immune responses and neurodegeneration influence disease susceptibility and progression. Circular RNAs (circRNAs) are emerging regulators of CNS and immune cell functions; however, the mechanisms underlying their regulation and dysregulation in MS remain poorly understood. Given the relevant role of sex-related differences in MS, in this pilot study we re-analyzed a previously published dataset by performing a sex-stratified analysis. Specifically, we focused on identifying circRNAs that are differentially expressed in female MS patients compared to male MS patients. We identified 33 differentially expressed circRNAs in peripheral blood mononuclear cells: 27 were more expressed and 6 were less expressed in female MS patients as compared to male MS patients. The discovery dataset was validated in an independent cohort of 8 female and 8 male relapsing-remitting (RR) MS patients confirming sex-dependent differences in the expression of five circRNAs. Among these, <i>hsa_circ_0140253</i> was significantly elevated, while <i>hsa_circ_0029426</i>,<i> hsa_circ_0005354</i>, and <i>hsa_circ_0002082</i> were significantly reduced. Notably, <i>hsa_circ_0140253</i> expression was markedly increased in patients with a higher level of disability and in progressive forms of MS, and across various disease-modifying therapies used in MS treatment. This exploratory study provides preliminary evidence of sex-related differences in circRNA expression in MS and their association with disease severity and DMT exposure. Our findings suggest that circRNA expression is influenced by multiple factors, underscoring the importance of considering sex and clinical variables in future studies. Further validation in larger cohorts is needed to confirm these observations and clarify the role of circRNAs in MS pathogenesis.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div><div><p>A sex-stratified analysis of PBMC samples from multiple sclerosis (MS) patients identifies distinct circRNA expression patterns between females and males. Sex-related circRNA differences are associated with disease severity and exposure to disease-modifying therapies. We identified 33 circRNAs differentially expressed between female and male MS patients, highlighting the increased levels in female of hsa_circ_0140253 and the reduction of hsa_circ_0029426, hsa_circ_0005354, and hsa_circ_0002082. These preliminary findings support the need for larger, sex-stratified and functional studies to better define the contribution of circRNAs to MS pathogenesis.</p></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025505","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":"In silico Genotype-Phenotype Correlation Analysis of Inherited Variations in Autism Spectrum Disorder Families Identify an Interplay between Sensory Function and Repetitive-behaviour Genes","authors":"Meghana Kommerahalli RameshRaju,&nbsp;Snijesh Valiya Parambath,&nbsp;Durbagula Srividhya,&nbsp;Bhagyalakshmi Shankarappa,&nbsp;Ramachandra Nallur Basappa,&nbsp;Ashitha S.Niranjana Murthy","doi":"10.1007/s12031-026-02542-9","DOIUrl":"10.1007/s12031-026-02542-9","url":null,"abstract":"<div><p>Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with a strong genetic basis. Most genetic studies on ASD emphasize de novo mutations, while inherited rare variants remain understudied. We hypothesize that subtle, inherited ASD-related traits accumulate across generations and clinically manifest as ASD in offspring. To investigate this, we extracted inherited variations from trio-based Whole Exome Sequences (WES) of 23 simplex ASD families (accession number PRJNA1071313 and PRJNA1072259). Data was processed in BWA, GATK and VarScan. Variants were annotated, filtered for functional impact, and scored using a ‘weighted scoring’ approach based on intolerance to genetic alterations. Overall 751 ‘weighted-genes’ with evolutionary and neuronal functions hosting deleterious inherited variations were functionally annotated for ASD-linked behaviours and comorbidities. We found 149 (20%) genes enriched for core ASD-behaviours like social-interaction and restrictive repetitive behaviours (RRB), 200 genes (26.6%) for associated-behaviours like hyperactivity, communication, intelligence and mood and 225 genes displayed neuronal-functions (<i>p</i> = 3.799E-20). Importantly, 62% of RRB genes displayed sensory functions and 71.43% of genes associated to social interaction deficits were also linked to seizures. Brain tissue expression analysis of all 751 genes revealed 95 prenatally and 195 postnatally upregulated genes were enriched with neurodevelopmental and neurotransmission functions, respectively; protein-protein-interactions suggested genes <i>BUB1</i>,<i> HMGA2</i>,<i> HDAC2</i>,<i> KALRN</i>,<i> SORL1</i>,<i> IGF2</i>,<i> FASN</i>,<i> WFS1</i> as promising new-candidates for ASD. In our ASD cohort, inherited variations in genes regulating sensory function and neurodevelopment were also RRB producing genes- supporting a multigenic, subdued but additive genetic load being passed down from unrelated parents to their offsprings- promising an underexplored avenue for autism genetic research.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148009585","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":"Dysfunction of the CD38-Miro1 Axis Disrupts Astrocyte-neuron Mitochondrial Transfer in Alzheimer’s Disease: Mechanisms and Therapeutic Restoration","authors":"Ahmed M. Abdelaziz,&nbsp;Mustafa M. Shokr,&nbsp;Mohamed K. Fathy,&nbsp;Mohamed N. Fawzy","doi":"10.1007/s12031-026-02531-y","DOIUrl":"10.1007/s12031-026-02531-y","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is characterized by early bioenergetic failure, contributing to synaptic dysfunction and neuronal vulnerability. This review examines a critical compensatory mechanism, the transfer of functional mitochondria from astrocytes to neurons, and its profound failure in AD. We detail the coordinated molecular cascade of this mitochondrial shunt, initiated by neuronal distress signals that activate astrocytic CD38. CD38-generated cyclic ADP-ribose triggers calcium release, which then binds to the mitochondrial Rho GTPase Miro1, modulating mitochondrial trafficking and promoting peripheral positioning via kinesin motor complexes for intercellular transport through tunneling nanotubes (TNTs). Transient, localized Ca²⁺ signals bias mitochondria toward docking at the plasma membrane for export, whereas sustained pathologic Ca²⁺ overload impairs trafficking via motor disengagement and Miro1 dysfunction. In AD, this rescue pathway is catastrophically disrupted by NAD+ depletion, Aβ-induced calcium dysregulation, tau-mediated microtubule instability, and oxidative stress, leading to inhibited CD38 signaling, Miro1 dysfunction/impairment, and TNT dismantlement. We systematically explain how this multi-level impairment initiates a vicious cycle of bioenergetic collapse. We also look at promising treatment options that could help restore this shunt, such as NAD+ augmentation to reactivate CD38, Miro1 stabilizers to help with trafficking, and interventions to keep TNT intact. Targeting the astrocyte-neuron mitochondrial shunt may represent an innovative, disease-modifying strategy that could transform the therapeutic framework from simple protein clearance to the proactive restoration of intercellular metabolic support, offering a promising direction for next-generation AD therapeutics.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148009584","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":"Hsa_circ_0065149 mediates the ceRNA network pathway: Research on the mechanism regulating myasthenia gravis","authors":"Siyu Liu,&nbsp;Qinghua Tian,&nbsp;Zhaojun Liu,&nbsp;Yingjie Ren,&nbsp;Aoqing Yu,&nbsp;Biying Chen,&nbsp;Tianyang Zhou,&nbsp;Xiang Li,&nbsp;Jianjian Wang,&nbsp;Lihua Wang,&nbsp;Huixue Zhang","doi":"10.1007/s12031-026-02544-7","DOIUrl":"10.1007/s12031-026-02544-7","url":null,"abstract":"<div><p>CircRNAs have been linked to the pathogenesis and progression of myasthenia gravis (MG), but research on this association remains limited. This study aims to provide a new perspective for understanding the molecular pathogenesis of MG. We obtained RNA-seq data from patients with acetylcholine receptor (AChR)-positive MG and healthy individuals from the Gene Expression Omnibus (GEO) database. A bioinformatics analysis was performed to identify differentially expressed circRNAs related to MG; the circRNA that was most consistently identified in most databases as a key factor involved in MG, hsa_circ_0065149, was chosen for further analysis. AChR localized at the postsynaptic membrane of the neuromuscular junction (NMJ) plays a pivotal role in mediating synaptic signal transmission. The CHRNA1 gene, which encodes the α1 subunit of AChR and is critical for its function—was subsequently selected as the target mRNA in our investigation, whereas our prediction pipeline identified miR-330-5p as the target. For functional assays, various constructs (e.g., hsa_circ_0065149-siRNA) were transfected as described in the Methods section. The qRT‒PCR results indicated that hsa_circ_0065149 knockdown significantly upregulated miR-330-5p and downregulated CHRNA1, while the inhibition of miR-330-5p significantly upregulated both hsa_circ_0065149 and CHRNA1. We also performed functional rescue experiments to confirm the regulatory hierarchical relationships among these factors. A dual-luciferase reporter assay confirmed that hsa_circ_0065149 and CHRNA1 are direct targets of miR-330-5p. These results suggest that hsa_circ_0065149 regulates MG by mediating the ceRNA network pathway, and we reasonably hypothesize that it may further contribute to the pathological process of MG by impairing signal transmission in the NMJ.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147985895","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":"Correction: Genetic Evidence Supports a Potential Role of WTAP-related m6A Regulation in Vascular Dementia: Insights from Mendelian Randomization and Multi-omics Analyses","authors":"Chengwan Zheng,&nbsp;Jin Qiu,&nbsp;Dehai Xian,&nbsp;Kaiwen Yang","doi":"10.1007/s12031-026-02543-8","DOIUrl":"10.1007/s12031-026-02543-8","url":null,"abstract":"","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979624","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":"Transcriptomic Analysis and Multiple Machine Learning Approaches Identify ZDHHC20 and Its Highly Correlated Gene AK5 as Biomarkers in Multiple System Atrophy","authors":"Zhipeng Lu,&nbsp;Zhongqi Li,&nbsp;Zhibiao Yin,&nbsp;Jialong Liu,&nbsp;Pu Fang","doi":"10.1007/s12031-026-02541-w","DOIUrl":"10.1007/s12031-026-02541-w","url":null,"abstract":"<div><p>Multiple system atrophy (MSA) is a fatal neurodegenerative disorder lacking effective diagnostic tools. While protein palmitoylation is crucial for neuronal function, its specific role in MSA pathogenesis remains unexplored. We integrated bulk and single-nucleus RNA sequencing (snRNA-seq) data from postmortem MSA brain tissues. Eight machine learning algorithms were utilized to screen palmitoylation-related genes. Downstream analyses, including functional enrichment, cellular deconvolution, and pseudotime trajectory inference, were then conducted. ZDHHC20 and its highly correlated gene, AK5, were identified as hub genes. Both demonstrated significant downregulation in MSA, particularly within the cerebellar white matter. Functional enrichment analysis linked this expression pattern to mitochondrial dysfunction and impaired energy metabolism. Furthermore, snRNA-seq revealed that ZDHHC20 and AK5 are predominantly expressed in oligodendrocytes and exhibit lower expression levels along the developmental trajectory in MSA compared to healthy controls. ZDHHC20 and AK5 represent promising biomarkers for MSA. These findings provide new insights into the diagnosis and treatment of MSA.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147959425","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}