Molecular Neurobiology最新文献

{"title":"Statin Use and Neuropathic Pain: Evidence from NHANES and Mendelian Randomization Analyses.","authors":"Zhixuan Lan, Liu Wang, Ruilin He, Zongbin Jiang","doi":"10.1007/s12035-026-05866-0","DOIUrl":"https://doi.org/10.1007/s12035-026-05866-0","url":null,"abstract":"<p><p>Neuropathic pain (NP) is a type of pain resulting from damage or dysfunction of the somatosensory system. Emerging evidence suggests that lipid-lowering drugs may influence the development or progression of NP. This study's objectives are to examine the association between statin use and diabetic peripheral neuropathy (DPN) using NHANES cross-sectional data, and to evaluate whether genetically proxied inhibition of HMGCR, PCSK9, and NPC1L1 is associated with DPN, trigeminal neuralgia (TN), and postherpetic neuralgia (PHN). In the NHANES component, we conducted a cross-sectional analysis of adults with diabetes and dyslipidemia from NHANES 1999-2004 to examine the association between statin use and DPN. In the primary analysis, dyslipidemia was defined using nonfasting/full-sample indicators, and an additional fasting-weight sensitivity analysis was performed using a broader fasting lipid definition. MR analyses were then performed to evaluate the associations of genetically proxied HMGCR, PCSK9, and NPC1L1 inhibition with DPN, TN, and PHN. In NHANES, statin use was not significantly associated with DPN in the primary analysis across progressively adjusted models, and the fasting-weight sensitivity analysis showed directionally similar but still non-significant results. By contrast, MR analyses suggested that genetically proxied HMGCR inhibition was associated with increased odds of DPN (OR = 4.20, 95% CI [2.42, 7.30]) and TN (OR = 1.52, 95% CI [1.14, 2.04]), PCSK9 inhibition with increased odds of DPN (OR = 4.85, 95% CI [2.64, 8.91]), and NPC1L1 inhibition with increased odds of TN (OR = 3.05, 95% CI [1.58, 5.91]). Evidence for PHN was inconsistent across analyses. The NHANES analyses did not identify a statistically significant association between statin use and DPN. By contrast, MR analyses suggested that genetically proxied HMGCR and PCSK9 inhibition may be associated with increased DPN risk, whereas HMGCR and NPC1L1 inhibition may be associated with TN. These associations warrant validation in independent populations and in studies with more precise neuropathic pain phenotyping.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817670","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":"miRNAs in Amyotrophic Lateral Sclerosis: Tiny Molecules, Tremendous Impact.","authors":"Sherif S Abdel Mageed, Ghadir A Sayed, Ahmed Mahdy, Walaa A El-Dakroury, Ahmed O Abdulkader, Hebatallah Ahmed Mohamed Moustafa, Reda M Mansour, Osama A Mohammed, Mohammed S Elballal, Ahmed E Elesawy, Ahmed S Doghish","doi":"10.1007/s12035-026-05880-2","DOIUrl":"https://doi.org/10.1007/s12035-026-05880-2","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder distinguished by progressive motor neuron degeneration, with diverse clinical manifestations and complex genetic and environmental triggers. The variability in disease progression underscores the necessity for tailored diagnostic and therapeutic approaches. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, have emerged as promising biomarkers and therapeutic targets in ALS. Dysregulation of specific miRNAs has been linked to mechanisms of ALS, including neuromuscular dysfunction, neuroinflammation, and neuronal survival/apoptosis. The potential of miRNA-based therapies, such as mimics and inhibitors, offers a more integrated approach by modulating entire disease networks, rather than targeting isolated pathways. However, challenges persist, particularly in delivering these therapies efficiently across the blood-brain barrier and minimizing off-target effects. Current delivery strategies involving nanoparticles, viral vectors, and exosome-based approaches require optimization for clinical use. This review synthesizes the latest research on miRNA-mediated mechanisms in ALS, evaluating their diagnostic, prognostic, and therapeutic potential, while highlighting the current limitations in clinical validation. It underscores the importance of standardized methodologies, multi-omics integration, and rigorous validation to facilitate the clinical translation of miRNA-based strategies. Standardized protocols and multicenter validation in large cohorts are essential to confirm the diagnostic accuracy of miRNAs, paving the way for their clinical application in ALS precision medicine.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817708","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":"Regulation of HSP90AA1/NRF2 by BDNF Contributes to the Attenuation of Rotenone-Induced Oxidative Stress in Parkinson's Disease Models.","authors":"Song Xie, Wanwan Cao, Jun Guo, Mengfan Zhao, Linxi Wang, Feiteng Liang, Zhao Wang","doi":"10.1007/s12035-026-05870-4","DOIUrl":"https://doi.org/10.1007/s12035-026-05870-4","url":null,"abstract":"<p><p>Parkinson's disease, a neurodegenerative disorder, is characterized by the degeneration of dopaminergic neurons and the accumulation of α-synuclein, both of which are aggravated by oxidative stress. This study utilized rotenone-treated SH-SY5Y cells to assess cell viability, ROS levels, and mitochondrial function. RNA-seq, mass spectrometry, and Co-IP analyses identified BDNF-regulated proteins linked to oxidative stress. In rotenone-induced PD mice, evaluations were made of motor performance, neuronal degeneration, and protein expression. Results showed that a 36-h exposure to 0.5 µM rotenone significantly increased ROS production, impaired mitochondrial function, and caused cellular damage in SH-SY5Y cells, effects which were reversed by BDNF overexpression. In mice, BDNF overexpression in the substantia nigra pars compacta alleviated PD-like symptoms. Co-IP analysis showed that BDNF modulates NRF2 and its associated proteins via HSP90AA1. These findings demonstrate that BDNF alleviates rotenone-induced oxidative stress in PD models through the HSP90AA1/NRF2 pathway, offering critical insights into the pathogenesis and potential therapeutic strategies for Parkinson's disease.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817683","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":"Stem Cell-Derived Exosomes Regulate Mitochondrial Function: A Novel Strategy for Parkinson's Disease Therapy.","authors":"Jinghan Wang, Cancan Wang, Xinyu Yuan, Jie Yan, Hongri Huang, Fujun Li, Yanqiu You, Zhongquan Qi","doi":"10.1007/s12035-026-05887-9","DOIUrl":"https://doi.org/10.1007/s12035-026-05887-9","url":null,"abstract":"<p><p>Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons, with mitochondrial dysfunction playing a critical role in its pathogenesis. As a critical organelle in eukaryotic cells, mitochondria not only serve as the central hub for energy metabolism but also play a pivotal role in regulating inflammation and cell apoptosis. However, mitochondrial damage leads to the accumulation of reactive oxygen species (ROS), oxidative stress, and abnormal aggregation of α-synuclein (α-Syn), which collectively contribute to neuronal injury and cell death. Therefore, targeting mitochondrial dysfunction has emerged as a promising therapeutic approach for PD. Exosomes, as extracellular vesicles (EVs) secreted by cells, encapsulate various substances, including proteins, nucleic acids, and lipids. Exosomes exhibit inherent targeting ability, high stability, and low immunogenicity. Additionally, the molecular contents within exosomes can regulate the biological responses of recipient cells by modulating cellular functions and signaling pathways. These characteristics of exosomes have contributed to significant achievements in the treatment of neurodegenerative diseases over the years. This review explores the latest advancements regarding the impact of stem cell-derived exosomes on mitochondrial function in PD, focuses on the regulation of mitochondrial dysfunction in recipient cells by the exosomal cargo, and presents recent evidence that suggests mitochondrial components within exosomes may facilitate cellular recovery. The aim is to provide new insights into potential therapeutic strategies for PD and to highlight directions for future research.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817677","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":"Impaired Development of the Medial Olivocochlear System in a KCNQ4-Deficient Mouse Model.","authors":"Ezequiel Rías, Ingrid Ouwerkerk, Guillermo Spitzmaul, Leonardo Dionisio","doi":"10.1007/s12035-026-05867-z","DOIUrl":"https://doi.org/10.1007/s12035-026-05867-z","url":null,"abstract":"<p><p>The medial olivocochlear (MOC) efferent system modulates outer hair cell (OHC) excitability and protects cochlea from overstimulation. Cholinergic activation of α9α10 nicotinic acetylcholine receptors (nAChRs) triggers Ca⁺² influx, activating BK and SK2 Ca⁺²-dependent K⁺ channels, and K⁺ extrusion through KCNQ4 to restore membrane potential. KCNQ4-loss causes chronic depolarization, OHC dysfunction, and hearing loss. Here, we investigated how KCNQ4 deficiency affects cochlear efferent synapse development and organization. Using confocal immunofluorescence, we analyzed efferent innervation in the organ of Corti of Kcnq4^-/- (KO) and Kcnq4^+/+ (WT) mice at 2, 3, 4, and 10 postnatal weeks (W). At 2 W, efferent terminals were similarly distributed between basal and lateral OHC membrane domains in both genotypes. During maturation, WT mice exhibited complete relocation of MOC terminals to the basal domain, whereas KO mice showed delayed maturation, with some terminals laterally displaced up to 10 W. KCNQ4 absence was associated with reduced number and volume of synaptic vesicles per efferent boutons on OHCs. Milder morphometric alterations were observed in efferent boutons within the inner hair cell region. At the molecular level, qPCR revealed downregulation of α10 nAChR subunit, BK, and SK2 transcripts in KO at 4 W, with recovery to 10 W. Despite this recovery, BK protein showed reduced expression, mislocalization, and disorganized synaptic plaques in OHCs. KO also displayed age-dependent upregulation of the calcium-binding proteins calbindin and calretinin, suggesting compensatory responses to altered Ca⁺² homeostasis. Together, these findings demonstrate that KCNQ4 is essential for OHC repolarization, maturation and maintenance of cochlear efferent synapses.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817687","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":"MicroRNA-mRNA Regulatory Network Associated with Cognitive Impairment in Multiple Sclerosis.","authors":"Bruna De Felice, Federica Farinella, Giuseppe Romano, Concetta Montanino, Simona Bonavita, Deborah Archetto, Elisabetta Maida, Simona Raimo, Giacomo Lus, Maria Cropano, Cinzia Coppola, Elisabetta Signoriello","doi":"10.1007/s12035-026-05893-x","DOIUrl":"https://doi.org/10.1007/s12035-026-05893-x","url":null,"abstract":"<p><p>Cognitive impairment (CI) is a frequent and disabling manifestation of multiple sclerosis (MS), yet its molecular underpinnings remain poorly understood. This study aimed to identify microRNA (miRNA) signatures and related gene expression changes associated with CI in MS. Forty-six people with MS underwent clinical, radiological, and cognitive assessment. Peripheral blood mononuclear cells were collected for miRNA profiling using the miRCURY LNA miRNA Focus PCR Panel and validated through RT-qPCR. Experimentally validated miRNA target genes were retrieved using miRWalk with miRTarBase filtering. Target networks were constructed in Cytoscape, followed by protein-protein interaction analysis using STRING and functional enrichment analysis with database for annotation, visualization, and integrated discovery (DAVID) ( https://davidbioinformatics.nih.gov/ ). Selected target genes were further evaluated by gene expression analysis. The results showed that three miRNAs (i.e., miR-146a-5p, miR-let-7a-5p, and miR-21-5p) were significantly dysregulated in patients with MS with CI compared to those with preserved cognition. Gene expression analysis identified differential regulations of IL-1B, IL-6, SLC16A10, and NEFL, supporting the involvement of inflammatory and neurodegenerative pathways. Correlation analyses indicated specific miRNA-mRNA relationships underlying these alterations. These findings suggest that the combined dysregulation of miR-146a-5p and miR-21-5p, together with their target genes, constitutes a molecular signature associated with CI in MS. This profile could contribute to the development of miRNA-based biomarkers for early detection and monitoring of cognitive dysfunction in MS.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817652","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":"Serum Vitamin E Levels in Multiple Sclerosis: Association with Diagnosis, Cognitive Function, Disability, and Depressive Symptoms.","authors":"Francesco Bruno, Patrizia Spadafora, Mario Luca Cuconati, Antonio Qualtieri, Ida Veltri, Selene De Benedittis, Beatrice Maria Greco, Annamaria Cerantonio, Luigi Citrigno, Gemma Di Palma, Olivier Gallo, Alberto Montesanto, Francesca Cavalcanti","doi":"10.1007/s12035-026-05878-w","DOIUrl":"10.1007/s12035-026-05878-w","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system and the most common neurodegenerative disease in young adults, characterized by motor, sensory, visual, and cognitive impairments. Vitamin E (α-Tocopherol), a fat-soluble antioxidant, may influence cognitive function, disability, and mood in MS. One hundred eighty-four Italian Caucasian MS patients and ninety-four healthy controls were included. Clinical and demographic variables were recorded, and serum vitamin E levels were measured by HPLC. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), disability with the Expanded Disability Status Scale (EDSS), and depressive symptoms with the Hamilton Depression Rating Scale (HDRS). Logistic and linear regression analyses were performed, adjusting for demographic, MS-related, and metabolic confounders. Bonferroni correction was applied. Discriminative ability for clinical cut-offs (MMSE ≤ 24, EDSS ≥ 6, HDRS ≥ 8) was assessed using receiver operating characteristic (ROC) curves. MS patients had significantly lower serum vitamin E levels compared to controls. Lower vitamin E levels were associated with MS diagnosis. In MS patients, higher vitamin E levels were associated with better cognitive performance and lower disability. All associations remained significant after Bonferroni correction in fully adjusted models. No significant relationship was found between vitamin E levels and depressive symptoms. Vitamin E showed good discriminative ability. Serum vitamin E levels showed significant associations with MS diagnosis, cognitive function, and disability, with good discriminative ability. Longitudinal studies are needed to clarify whether low vitamin E levels influence the risk of developing MS, while randomized controlled trials are warranted to determine whether vitamin E supplementation may provide clinical benefits.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776638","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":"Micro- and Nanoplastics in the Human Brain: Mechanistic Plausibility, Translational Challenges, and Links to Neurological Disease Trends.","authors":"Farshid Ghiyamihoor, Azam Asemi Rad, Parya Hassanifar, Raj Kaur, Janvi Hitenkumar Patel, Ian Kim, Asghar Marzban, Mehdi Mehdizadeh, David B Levin, Saeid Ghavami, Antoniya Toncheva, Samira Benali, Philippe Dubois, Fuat Balci, Hamid R Habibi, Mario Manto, Hassan Marzban","doi":"10.1007/s12035-026-05895-9","DOIUrl":"https://doi.org/10.1007/s12035-026-05895-9","url":null,"abstract":"<p><p>The exponential growth in plastic production since the mid-twentieth century has led to the pervasive presence of micro- and nanoplastics (MNPs) across ecosystems and human exposure pathways, coinciding with a rising global burden of neurological disorders. Increasing evidence demonstrates that MNPs are not confined to peripheral tissues but can accumulate even in the human brain, raising concerns about their potential contribution to neurological disease. This structured review synthesizes global trends in plastic production, environmental MNP burden, and human exposure, together with emerging data on brain accumulation, entry pathways, neurotoxic mechanisms, and key translational challenges. We present evidence showing that MNPs may cross brain barriers via multiple routes, including the blood-brain barrier, blood-cerebrospinal fluid barrier, olfactory, and circumventricular pathways, particularly under conditions of barrier vulnerability. Experimental studies reveal that once in neural tissue, MNPs may disrupt synaptic function, mitochondrial homeostasis, autophagy, and redox balance, while activating neuroinflammatory and gut-brain axis-mediated pathways. These mechanisms intersect with disease-relevant processes implicated in multiple neurological disorders whose global prevalence and societal burden have sharply increased over recent decades, including stroke, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, mood disorders, and neurodevelopmental conditions. Despite growing mechanistic plausibility, translational and human epidemiological evidence remains limited by methodological heterogeneity, a lack of standardized detection methods, and the absence of longitudinal clinical data/studies. We highlight critical analytical and translational gaps, public health implications, and priorities for longitudinal, biomarker‑driven studies needed to rigorously test whether MNPs may contribute to population‑level risk of neurological disease.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776476","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":"Uncovering Spatiotemporal and Functional Dynamics of Long Non-coding RNAs During Alzheimer's Progression in the Human Brain at Single-Cell Resolution.","authors":"Allan de Carvalho, Izabela Mamede, Leonardo Sanches, Guilherme Juvenal, Fernanda Tibolla Viero, Gloria Regina Franco, Yong Tang, Eduardo Moraes Reis, Henning Ulrich","doi":"10.1007/s12035-026-05859-z","DOIUrl":"10.1007/s12035-026-05859-z","url":null,"abstract":"<p><p>Increasing prevalence of Alzheimer's disease, driven by population aging, highlights the need to investigate its underlying molecular mechanisms. Within this context, long non-coding RNAs (lncRNAs) have emerged as a key regulatory layer. To advance the understanding of lncRNA dysregulation and function during Alzheimer's disease progression, we reanalyzed publicly available single-nucleus RNA sequencing (snRNA-seq) datasets. The selected transcriptomic datasets were integrated and subjected to differential expression and genomic co-localization correlation analyses to infer putative cis-regulatory mechanisms. Our results reveal conserved cell-type composition and a shared transcriptional trajectory across brain regions during Alzheimer's disease progression. In contrast, lncRNAs displayed marked cell-type and context specificity and formed coordinated expression patterns with neighboring genes within defined chromatin contexts. These associations suggest potential cis-regulatory roles and implicate lncRNAs in processes such as synaptic plasticity and maladaptive oligodendrocyte differentiation linked to myelin dysfunction. While these findings are primarily hypothesis-generating, they provide a cross-regional framework and a prioritized set of candidate lncRNAs for future functional investigation in Alzheimer's disease.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775974","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":"MyomiR Networks in Spinal Muscular Atrophy: Associations With Clinical Severity and Treatment Response.","authors":"Maruša Barbo, Blaž Koritnik, Lea Leonardis, Vita Dolžan, Metka Ravnik-Glavač","doi":"10.1007/s12035-026-05862-4","DOIUrl":"https://doi.org/10.1007/s12035-026-05862-4","url":null,"abstract":"<p><p>Disease-modifying therapies have significantly influenced the clinical course of spinal muscular atrophy (SMA), yet objective biomarkers for monitoring disease progression and treatment remain limited. We profiled four muscle-specific miRNAs (myomiRs), ten bioinformatically predicted mRNA targets, two functionally associated lncRNAs, and SMN transcripts in whole blood from 50 adults with SMA types II-IV. Using RT-qPCR, we assessed associations between baseline RNA expression and demographic and clinical parameters, including SMA type, ambulatory status, motor and respiratory function, and explored longitudinal changes during nusinersen (24 months) and risdiplam (6/12 months) treatment. At baseline, miR-206 was higher in type III than in type II and in ambulatory compared to non-ambulatory patients, while it correlated positively with motor and respiratory function and with SMN mRNA variants (total, FL, and ∆7). SMN transcript levels were higher in patients with more SMN2 copies and in ambulatory patients and showed positive correlations with motor and respiratory function. miR-133a-3p and miR-133b correlated negatively with upper limb and respiratory function, and sex-related differences were observed for miR-133a-3p, FGFR1, ANXA2, and LINCMD1. During nusinersen treatment, we observed a decrease in miR-206, LINCMD1, and lnc-GJA1-2, alongside modest reductions in SMN-∆7 and total SMN. In contrast, risdiplam induced a peripheral splicing shift: SMN-FL and the FL/∆7 ratio increased, while SMN-∆7 decreased; miR-133a-3p also decreased at 6 months. By integrating muscle-derived RNAs, particularly miR-206, with blood SMN2 splicing changes, we propose a composite, blood-based biomarker approach for assessing SMA status and treatment-associated molecular changes and highlight myomiR-lncRNA-mRNA networks that suggest disease-relevant mechanisms.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817680","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}