{"title":"Empowering limited-resource countries: collaborating with expert centers for diagnosis of primary ciliary dyskinesia.","authors":"Mine Yuksel Kalyoncu, Rim Hjeij, Muruvvet Yanaz, Aynur Gulieva, Merve Selcuk Balcı, Şeyda Karabulut, Neval Metin Cakar, Almala Pınar Ergenekon, Ela Erdem Eralp, Yasemin Gokdemir, Heymut Omran, Bülent Taner Karadag","doi":"10.3389/fmolb.2025.1547152","DOIUrl":"10.3389/fmolb.2025.1547152","url":null,"abstract":"<p><strong>Introduction: </strong>Primary ciliary dyskinesia (PCD) is an autosomal recessive rare disease caused by alterations in ciliary structure and function. Without a unique gold standard diagnostic test, the European Respiratory Society and the American Thoracic Society recommend using various diagnostic techniques to improve accuracy. This study aimed to demonstrate the effectiveness of immunofluorescence (IF) analysis in the diagnosis of PCD cases with uncertain genetic results and to demonstrate the importance of international collaboration in the diagnosis of PCD.</p><p><strong>Methods: </strong>In collaboration with IF specialists at the University of Münster, individuals with inconclusive results in the Marmara University PCD panel consisting of the 22 most common genes and clinically suggestive of PCD were included in the study. IF imaging determined the subcellular localization of DNAH5 and GAS8 in respiratory epithelial cells. Nasal nitric oxide measurements, high-speed video microscopy (HSVM) analysis, and genetic analyses were performed.</p><p><strong>Results: </strong>19 patients were evaluated. The median age (25-75p) was 15 years (10-20 years) with 12 (63.2%) males. Three cases (15.7%) showed an absence of DNAH5, and one (5.3%) had a proximal distribution of DNAH5 in the ciliary axoneme. One case (5.3%) had cells without cilia, indicating a possible ciliogenesis defect. All individuals with abnormal IF analysis had a PICADAR score of 6 or above, and their cilia were immotile in HSVM.</p><p><strong>Discussion: </strong>Consistent with the IF finding suggesting a ciliogenesis defect, further genetic analysis revealed biallelic pathogenic variants in CCNO in the affected individual. The absence of DNAH5 in the respiratory epithelial cells of an individual carrying heterozygous pathogenic splice variants in DNAH5 suggests the need for further genetic analysis. This study underscores the importance of international collaboration in diagnosing rare diseases like PCD.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1547152"},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriel Santos Arini, Tiago Cabral Borelli, Elthon Góis Ferreira, Rafael de Felício, Paula Rezende-Teixeira, Matheus Pedrino, Franciene Rabiço, Guilherme Marcelino Viana de Siqueira, Luiz Gabriel Mencucini, Henrique Tsuji, Lucas Sousa Neves Andrade, Leandro Maza Garrido, Gabriel Padilla, Alberto Gil-de-la-Fuente, Mingxun Wang, Norberto Peporine Lopes, Daniela Barretto Barbosa Trivella, Letícia Veras Costa-Lotufo, María-Eugenia Guazzaroni, Ricardo Roberto da Silva
{"title":"A multi-omics reciprocal analysis for characterization of bacterial metabolism.","authors":"Gabriel Santos Arini, Tiago Cabral Borelli, Elthon Góis Ferreira, Rafael de Felício, Paula Rezende-Teixeira, Matheus Pedrino, Franciene Rabiço, Guilherme Marcelino Viana de Siqueira, Luiz Gabriel Mencucini, Henrique Tsuji, Lucas Sousa Neves Andrade, Leandro Maza Garrido, Gabriel Padilla, Alberto Gil-de-la-Fuente, Mingxun Wang, Norberto Peporine Lopes, Daniela Barretto Barbosa Trivella, Letícia Veras Costa-Lotufo, María-Eugenia Guazzaroni, Ricardo Roberto da Silva","doi":"10.3389/fmolb.2025.1515276","DOIUrl":"10.3389/fmolb.2025.1515276","url":null,"abstract":"<p><strong>Introduction: </strong>Exploiting microbial natural products is a key pursuit of the bioactive compound discovery field. Recent advances in modern analytical techniques have increased the volume of microbial genomes and their encoded biosynthetic products measured by mass spectrometry-based metabolomics. However, connecting multi-omics data to uncover metabolic processes of interest is still challenging. This results in a large portion of genes and metabolites remaining unannotated. Further exacerbating the annotation challenge, databases and tools for annotation and omics integration are scattered, requiring complex computations to annotate and integrate omics datasets.</p><p><strong>Methods: </strong>Here we performed a two-way integrative analysis combining genomics and metabolomics data to describe a new approach to characterize the marine bacterial isolate BRA006 and to explore its biosynthetic gene cluster (BGC) content as well as the bioactive compounds detected by metabolomics.</p><p><strong>Results and discussion: </strong>We described BRA006 genomic content and structure by comparing Illumina and Oxford Nanopore MinION sequencing approaches. Digital DNA:DNA hybridization (dDDH) taxonomically assigned BRA006 as a potential new species of the Micromonospora genus. Starting from LC-ESI(+)-HRMS/MS data, and mapping the annotated enzymes and metabolites belonging to the same pathways, our integrative analysis allowed us to correlate the compound Brevianamide F to a new BGC, previously assigned to other function.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1515276"},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Hossein Ataee, Seyed Ali Mirhosseini, Reza Mirnejad, Hamideh Mahmoodzadeh Hosseini, Jafar Amani
{"title":"Comparison of two immunotoxins against DLL3 receptor; as an inhibitor for small cell lung cancer.","authors":"Mohammad Hossein Ataee, Seyed Ali Mirhosseini, Reza Mirnejad, Hamideh Mahmoodzadeh Hosseini, Jafar Amani","doi":"10.3389/fmolb.2025.1506768","DOIUrl":"10.3389/fmolb.2025.1506768","url":null,"abstract":"<p><p>Despite the efforts of researchers to develop new treatments for small cell lung cancer (SCLC), achieving effective treatment has not yet happened. Targeted therapy utilizing delta-like ligand 3 (DLL3), which is highly expressed in SCLC patients, holds promise as a potential solution. Immunotoxins, consisting of bacterial toxins from the ADP-ribosyl transferase toxin family have shown effectiveness in targeting cancer cells. In this study, we investigated the binding ability, cytotoxicity, apoptosis induction rate, and permeability of two immunotoxins based on the rovalpituzumab antibody. The binding ability of immunotoxins to the receptor was performed by the Cell-ELISA method. Following this, the cell viability of cancer and normal cells immunotoxins was evaluated using the MTT assay. The ability to induce apoptosis and the penetration of immunotoxins was assessed by flow cytometry and Western blotting method. The binding ability of the immunotoxin Rova-Typh to the DLL3 receptor was higher compared to the immunotoxin Rova-GrB. The cell viability of A549 cancer cells treated with immunotoxins showed IC50 concentrations of 338 and 734 nM for immunotoxins Rova-GrB and Rova-Typh, respectively. The induction of apoptosis by immunotoxin Rova-Typh was greater compared to immunotoxin Rova-GrB. The designed immunotoxins in prokaryotic hosts exhibit good anticancer performance in A549 lung cancer cells. Additionally, the bacterial toxin-based immunotoxin has a greater ability to induce apoptosis compared to human enzymes and can be considered as a therapeutic option for SCLC cancer.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1506768"},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Computational molecular insights into ibrutinib as a potent inhibitor of HER2-L755S mutant in breast cancer: gene expression studies, virtual screening, docking, and molecular dynamics analysis.","authors":"Tamizhini Loganathan, C George Priya Doss","doi":"10.3389/fmolb.2025.1510896","DOIUrl":"10.3389/fmolb.2025.1510896","url":null,"abstract":"<p><strong>Background: </strong>The proposed study integrates several advanced computational techniques to unravel the molecular mechanisms underlying breast cancer progression and drug resistance.</p><p><strong>Methods: </strong>We investigated HER2-L755S mutation through a multi-step approach, including gene expression analysis, molecular docking, and molecular dynamics simulations.</p><p><strong>Results and discussion: </strong>By conducting a network-based analysis of gene expression data from breast cancer samples, key hub genes such as <i>MYC, EGFR, CDKN2A, ERBB2, CDK1, E2F1, TOP2A, MDM2, TGFB1,</i> and <i>FOXM1</i> were identified, all of which are critical in tumor growth and metastasis. The study mainly focuses on the ERBB2 gene, which encodes the HER2 protein, and its common mutation HER2-L755S, associated with breast cancer and resistance to the drug lapatinib. The HER2-L755S mutation contributes to both tumorigenesis and therapeutic failure. To address this, alternative therapeutic strategies were investigated using combinatorial computational approaches. The stability and flexibility of the HER2-L755S mutation were evaluated through comparative molecular dynamics simulations over 1000 ns using Gromacs in the unbound (Apo) state. Virtual screening with Schrodinger Glide identified ibrutinib as a promising alternative to lapatinib for targeting the HER2-L755S mutant. Detailed docking and molecular dynamics simulations in the bound (Holo) state demonstrated that the HER2-L755S-ibrutinib complex exhibited higher binding affinity and lower binding energy, indicating more stable interactions compared to other complexes. MM-PBSA analysis revealed that the HER2-L755S-ibrutinib complex had more negative binding energy than the HER2-L755S-afatinib, HER2-L755S-lapatinib, and HER2-L755S-neratinib complexes, suggesting that ibrutinib forms the most stable complex with favorable binding interactions.</p><p><strong>Conclusion: </strong>These results provide in-depth atomic-level insights into the binding mechanisms of these inhibitors, highlighting ibrutinib as a potentially effective inhibitor for the clinical treatment of breast cancer.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1510896"},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of aging on calcium channels in skeletal muscle.","authors":"Mingyi Dong, Andrés Daniel Maturana","doi":"10.3389/fmolb.2025.1558456","DOIUrl":"10.3389/fmolb.2025.1558456","url":null,"abstract":"<p><p>In skeletal muscle, calcium is not only essential to stimulate and sustain their contractions but also for muscle embryogenesis, regeneration, energy production in mitochondria, and fusion. Different ion channels contribute to achieving the various functions of calcium in skeletal muscles. Muscle contraction is initiated by releasing calcium from the sarcoplasmic reticulum through the ryanodine receptor channels gated mechanically by four dihydropyridine receptors of T-tubules. The calcium influx through store-operated calcium channels sustains the contraction and stimulates muscle regeneration. Mitochondrial calcium uniporter allows the calcium entry into mitochondria to stimulate oxidative phosphorylation. Aging alters the expression and activity of these different calcium channels, resulting in a reduction of skeletal muscle force generation and regeneration capacity. Regular physical training and bioactive molecules from nutrients can prevent the effects of aging on calcium channels. This review focuses on the current knowledge of the effects of aging on skeletal muscles' calcium channels.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1558456"},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingxing Fan, Ran Lu, Jiayuan Wu, Jie Huang, Yanming Fang
{"title":"Osteoporotic vertebral fractures and subsequent fractures: risk factors from a retrospective observational study of patients with osteoporosis.","authors":"Mingxing Fan, Ran Lu, Jiayuan Wu, Jie Huang, Yanming Fang","doi":"10.3389/fmolb.2025.1558052","DOIUrl":"10.3389/fmolb.2025.1558052","url":null,"abstract":"<p><strong>Purpose: </strong>Osteoporosis is a progressive, systemic, skeletal disorder characterized by increased bone fragility and susceptibility to fracture. Prior fractures are a strong predictor of subsequent fractures, but it is essential to identify further clinical and demographic characteristics of patients with osteoporosis that are associated with subsequent fracture risk.</p><p><strong>Methods: </strong>In this retrospective observational cohort study, male and female patients over the age of 55 years with osteoporosis who experienced vertebral fractures between 2019 and 2021 were included. All patients' basic clinical data, serum biochemical and bone turnover markers, bone mineral density, and other indicators were recorded uniformly. The incidence of subsequent fractures during the two-year follow-up period was analyzed. Independent risk factors for subsequent fractures were identified by binary logistic regression analysis.</p><p><strong>Results: </strong>A total of 1,096 patients were included. Of these, 311 (28.4%) patients suffered a subsequent fracture during the two-year follow-up period. The incidences of subsequent fracture sites were 18.4% vertebral, 14.2% forearm/wrist/hand, and 9.9% hip/femur. Compared with the non-subsequent fracture group (non-SFG), binary logistic regression analysis showed that body mass index (BMI) (OR [95% CI] 0.825 [0.720-0.945]; P = 0.006), femoral neck bone mineral density (BMD) T-score (OR [95% CI] 0.067 [0.012-0.385]; P = 0.002), and C-terminal telopeptide of type 1 collagen (CTX) levels (OR [95% CI] 6.089 [1.735-21.375]; P = 0.005) were independent risk factors associated with subsequent fractures.</p><p><strong>Conclusion: </strong>Patients with osteoporosis and previous vertebral fractures are at a higher risk of further fractures at a two-year follow-up period. BMI, femoral neck BMD T-score, and CTX levels were independent risk factors for refracture. Integrating BMI, femoral neck BMD, and CTX levels into an individualized care plan for patients with osteoporotic vertebral fractures may help prevent subsequent fractures in high-risk populations.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1558052"},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Sida cordifolia</i> is efficacious in models of Huntington's disease by reducing ER stress.","authors":"Prasanna K Simha, Chandramouli Mukherjee, Vikas Kumar Gupta, Karishma Bhatia, Padmanabhi Nagar, Azeem Nazeer Za, Ashwini Godbole, Bhavani Shankar Sahu, Sanjeev K Upadhyay","doi":"10.3389/fmolb.2025.1567932","DOIUrl":"10.3389/fmolb.2025.1567932","url":null,"abstract":"<p><p>Neurodegenerative disorders (NDs) are a major class of diseases where modern science has not succeeded in providing solutions to the desired levels. ER stress pathway is implicated in pathophysiology of several neurodegenerative disorders, especially those classified as proteinopathies. Several traditional medicines are used to treat neurodegeneration and <i>Sida cordifolia</i> (SC) is one of the common ingredients in formulations used for treating NDs and neuropathic pain. However, the mode of action is not clear. We studied the effectiveness of SC in Huntington's Disease (HD) model using <i>Caenorhabditis elegans</i> and mammalian cells. We used a transgenic <i>C. elegans</i> that expresses mutant huntingtin protein tagged with Yellow Fluorescent Protein (YFP) in their body wall muscle. In <i>C. elegans</i>, SC not only improved motility but also substantially increased the life span. Cell-based studies using inducible mutant Huntingtin protein (mHTT) with a long polyQ tail tagged with EGFP showed that SC profoundly modulates ER stress, reducing the stress caused by mHTT protein. The study showed that the mode of action of SC, at least partially, is through modulation of ER stress pathway, thereby normalizing the changes brought about by overexpression of mHTT.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1567932"},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biomarkers in glioblastoma and degenerative CNS diseases: defining new advances in clinical usefulness and therapeutic molecular target.","authors":"Fan Bu, Jifa Zhong, Ruiqian Guan","doi":"10.3389/fmolb.2025.1506961","DOIUrl":"10.3389/fmolb.2025.1506961","url":null,"abstract":"<p><strong>Background: </strong>Discovering biomarkers is central to the research and treatment of degenerative central nervous system (CNS) diseases, playing a crucial role in early diagnosis, disease monitoring, and the development of new treatments, particularly for challenging conditions like degenerative CNS diseases and glioblastoma (GBM).</p><p><strong>Methods: </strong>This study analyzed gene expression data from a public database, employing differential expression analyses and Gene Co-expression Network Analysis (WGCNA) to identify gene modules associated with degenerative CNS diseases and GBM. Machine learning methods, including Random Forest, Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine - Recursive Feature Elimination (SVM-RFE), were used for case-control differentiation, complemented by functional enrichment analysis and external validation of key genes.</p><p><strong>Results: </strong>Ninety-five commonly altered genes related to degenerative CNS diseases and GBM were identified, with <i>RELN</i> and <i>GSTO2</i> emerging as significant through machine learning screening. Receiver operating characteristic (ROC) analysis confirmed their diagnostic value, which was further validated externally, indicating their elevated expression in controls.</p><p><strong>Conclusion: </strong>The study's integration of WGCNA and machine learning uncovered <i>RELN</i> and <i>GSTO2</i> as potential biomarkers for degenerative CNS diseases and GBM, suggesting their utility in diagnostics and as therapeutic targets. This contributes new perspectives on the pathogenesis and treatment of these complex conditions.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1506961"},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of a neuron-specific ferroptosis in the neurodegenerative mucopolysaccharidosis III model.","authors":"Mathilde Larribau, Myriam Rouahi, Christophe Santiago, Jérôme Ausseil, Zoubida Karim","doi":"10.3389/fmolb.2025.1476513","DOIUrl":"10.3389/fmolb.2025.1476513","url":null,"abstract":"<p><p>Sanfilippo syndrome (MPSIII) is a neurodegenerative disorder caused by enzyme deficiencies, leading to the toxic accumulation of heparan sulfate oligosaccharides in the brain. Emerging evidence suggests that ferroptosis, an iron-dependent form of cell death, contribute to neurodegeneration. To investigate ferroptosis in MPSIIIB, we examined its regulatory mechanisms and markers in MPSIIIB brains. Our results showed elevated iron levels, decreased mRNA expression of TFR1 and ZIP14 (involved in iron uptake) at 9 months of age, and increased protein levels of FTH (which stores intracellular iron) in MPSIIIB brains, indicating a potential link to ferroptosis. We also observed diminished levels of ferroptosis-neutralizing proteins (xc-/GPX4), while the protective pathway (Keap1-Nrf2) was activated. Oxidative homeostasis disruption was revealed by increased expression of genes encoding SOD2, SIRT3, iNOS, and nNOS enzymes. Increased expression of lipid peroxidation genes (ascl4 and lpcat3) further supported ferroptosis involvement. Furthermore, we analyzed protein abundance and brain immunostaining of the iron exporter FPN. Despite its high expression levels, this protein appeared misfolded and was insufficiently targeted to cellular plasma membrane, which might contribute to cellular iron retention. The co-localization of FPN with NeuN, a marker of neurons, demonstrates that only neurons are affected by this targeting defect, suggesting neuronal ferroptosis specifically in MPSIIIB. Overall, our findings evidenced of the involvement of ferroptosis in MPSIIIB pathogenesis, highlighting dysregulation in iron homeostasis, antioxidant defenses, and lipid peroxidation as key features of the disease.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1476513"},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}