Novel Phenotypical and Biochemical Findings in Mucolipidosis Type II

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2408 - 2408

Опубликована: Март 7, 2025

Mucolipidosis type II is a very rare lysosomal disease affecting the UDP-GlcNAc N-acetylglucosamine-1-phosphotransferase enzyme, which catalyzes synthesis of targeting signal mannose 6-phosphate in acid hydrolases. Its deficiency hinders arrival enzymes to lysosome, diminishing multiple degradations components that cells need perform. Due low prevalence this condition, available information scarce. This article aims deepen understanding disease; clinical, biochemical, and proteomic data are analyzed. Three patients have been identified presenting GNPTAB pathogenic variants using whole exome sequencing. A biochemical profile for these has carried out through quantification glycosaminoglycans urine samples enzymatic analysis dried blood spot (DBS) samples. Quantitative studies were performed. Results show how assays DBS can be used diagnose both during neonatal period or more advanced age. Increased levels sphingomyelinase, alpha-iduronidase, iduronidate 2-sulfatase, alpha-N-acetyl glucosaminidase, beta-glucuronidase found. Conclusion: method could potentially improve early diagnosis. Proteomic supporting results reveal disrupted pathways, including degradation dermatan sulfate, heparan cellular cholesterol trafficking.

Язык: Английский

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Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 6024 - 6024

Опубликована: Май 30, 2024

Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events endothelial dysfunction. In spite efficacy demonstrated by enzyme replacement therapy pharmacological chaperones in delaying progression, few studies have analyzed whether these treatments can improve pro-inflammatory state FD patients. Therefore, aim this work was assess cytokines cardiovascular risk-related proteins detectable plasma from patients, treated not with ERT, evaluate reliability markers monitoring stage treatment effects. We identified dysfunction (ADAMTS-13, TNF-α, GDF-15, MIP-1β, VEGFA, MPO, MIC-1) that cooperate common pathway are increased patients’ samples. As shown assessment over time, they help risk higher severity FD, well ERT Even though cannot be considered proper biomarkers due their non-specificity taken together provide signature reference molecules prognostic value for early diagnosis, evaluation progression efficacy, using blood

Язык: Английский

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Role of the Innate Immune Response in Glomerular Disease Pathogenesis: Focus on Podocytes

Cells, Год журнала: 2024, Номер 13(13), С. 1157 - 1157

Опубликована: Июль 6, 2024

Accumulating evidence indicates that inflammatory and immunologic processes play a significant role in the development progression of glomerular diseases. Podocytes, terminally differentiated epithelial cells, are crucial for maintaining integrity filtration barrier. Once injured, podocytes cannot regenerate, leading to progressive proteinuric However, emerging suggests not only maintain barrier important targets immune responses but also exhibit many features immune-like where they involved modulation activity innate adaptive immunity. This dual may lead discovery new therapeutic treating review aims provide an overview immunity mechanisms podocyte injury

Язык: Английский

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Inflammation, Oxidative Stress, and Endothelial Dysfunction in the Pathogenesis of Vascular Damage: Unraveling Novel Cardiovascular Risk Factors in Fabry Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8273 - 8273

Опубликована: Июль 29, 2024

Anderson-Fabry disease (AFD), a genetic disorder caused by mutations in the α-galactosidase-A

Язык: Английский

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Sex Differences in Circulating Inflammatory, Immune, and Tissue Growth Markers Associated with Fabry Disease-Related Cardiomyopathy

Cells, Год журнала: 2025, Номер 14(5), С. 322 - 322

Опубликована: Фев. 20, 2025

Fabry disease (FD) is a lysosomal disorder due to alpha-galactosidase-A enzyme deficiency, accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) which lead proinflammatory effects. Males develop progressive hypertrophic cardiomyopathy (HCM) followed by fibrosis; females nonconcentric hypertrophy and/or early fibrosis. The inflammatory response Gb3/lyso-Gb-3 one the suggested pathogenic mechanisms in FD when secretion transforming growth factors with infiltration lymphocytes macrophages into tissue promotes cardiofibrosis. This study aims evaluate inflammation-driving cytokines cardio-hypertrophic remodeling biomarkers contributing sex-specific HCM progression. Biomarkers were studied 20 healthy subjects 45 patients. IL-2, IL-10, TNF-α, IFN-γ elevated all patients, while IL-1α, MCP-1, TNFR2 showed differences. increased associated NF-kB pathway males HCM, revealing correlation between IFN-γ, VEGF, GM-CSF, IL-2. In female impaired TNFα/TNFR2/TGFβ cluster correlations IL-1α was observed. activation indicates significant inflammation during males. signaling may explain fibrosis cardiomyopathy. Sex-specific responses influence severity progression HCM.

Язык: Английский

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A Multi-Omics-Empowered Framework for Precision Diagnosis and Treatment of Lysosomal Diseases

Journal of Pharmaceutical Analysis, Год журнала: 2025, Номер unknown, С. 101274 - 101274

Опубликована: Март 1, 2025

Язык: Английский

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Disrupted synaptic gene expression in Fabry disease: Findings from RNA sequencing

Neurobiology of Disease, Год журнала: 2025, Номер 209, С. 106908 - 106908

Опубликована: Апрель 14, 2025

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by deficiency in the enzyme α-galactosidase A. This defect leads to progressive accumulation of glycosphingolipids, resulting kidney, heart, and nervous system damage, which contributes significant morbidity mortality. Early diagnosis essential prevent irreversible damage optimize treatment strategies. Recent research aims provide better understanding FD pathophysiology improve management approaches. study an international, multicenter, cross-sectional analysis that used RNA sequencing (RNA-seq) compare blood samples from 50 patients age- sex-matched healthy controls. The objective was identify gene expression patterns investigate secondary cellular pathways affected dysfunction. Among more than 400 differentially expressed genes detected, 207 were protein-coding genes, most overexpressed cohort. Functional enrichment highlighted processes related synaptic function, specifically concerning chemical transmission membrane potential regulation. Identified included those voltage-gated ion channels, neurotransmitter receptors, cell adhesion molecules, scaffold proteins, proteins associated with vesicles neurotrophic signaling, all linked lipid rafts. Notable identified encoding potassium channel (KCNQ2, KCNQ3, KCNMA1) ionotropic receptor involved glutamatergic (GRIN2A, GRIN2B) GABAergic systems (GABRA4, GABRB1, GABRG2, GABRQ). These findings suggest dysfunction defects FD, paving way for further into role pathology rafts underlying pathogenesis clinical outcomes FD.

Язык: Английский

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Characterisation of the periodontal proteome in gingival crevicular fluid and saliva using SWATH-MS

Frontiers in Cellular and Infection Microbiology, Год журнала: 2025, Номер 15

Опубликована: Май 2, 2025

Introduction Proteomic techniques are useful to analyse the periodontal proteome in gingival crevicular fluid (GCF) and saliva. However, few investigations have assessed compared GCF salivary proteomes. Therefore, this research aims structure compare protein expression these fluids between individuals with health those periodontitis. Methods saliva were collected from 44 periodontally healthy subjects 41 periodontitis (stages III-IV). Samples analysed using sequential window acquisition of all theoretical mass spectra (SWATH-MS), proteins identified employing UniProt database. The was principal component analysis (PCA). Differential defined as an adjusted p-value <0.05 combined a fold-change ≥2 (upregulated) or ≤0.5 (downregulated). Results 250 abundant quantified 377 (238 common). different both oral fluids. In GCF, 63 (25.2%) differentially expressed, 38 upregulated 25 downregulated most overexpressed haemoglobin subunits (Hbs) beta (fold-change 5.06) alpha (4.35), carbonic anhydrase 1 (4.28), S100-P (4.27). Among underexpressed proteins, 14 keratins, type II cytoskeletal 6B being (0.10), together glyceraldehyde-3-phosphate dehydrogenase (0.12) zymogen granule 16 homolog B (0.13). saliva, 59 (15.7%) 55 four Twenty-nine showed ≥4, highlighting beta-2-microglobulin (44.14), keratin, I 13 (36.23), neutrophil defensin (25.08), S100-A9 (12.30), A8 (10.61), A12 (4.76), P (4.72), annexin A1 (9.34), lysozyme C (4.98), immunoglobulin heavy constant (4.45), resistin (4.37), Hbs (4.20) (4.06). lipocalin-1 (0.35). Fourteen expressed where seven keratins but Conclusion Periodontitis alters numerous vary qualitatively quantitatively, indicating patterns

Язык: Английский

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Comparative Brain Proteomic Analysis between Sham and Cerebral Ischemia Experimental Groups

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7538 - 7538

Опубликована: Июль 9, 2024

Sham control groups are essential in experimental animal studies to reduce the influence of surgical intervention. The intraluminal filament procedure is one most common models middle cerebral artery occlusion (MCAO) used study brain ischemia. However, a sham group usually not included design these studies. In this study, we aimed evaluate relevance by analyzing and comparing protein profiles MCAO groups. group, 98 dysregulated proteins were detected, compared 171 ischemic group. Moreover, comparative revealed existence pool 57 that appeared be both animals. These results indicated required for (MCA) induces changes expression associated with lesions. This highlights importance including design, ensure intervention does affect therapeutic target under study.

Язык: Английский

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The proteome of circulating extracellular vesicles and their functional effect on platelets vary with the isolation method

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 20, 2024

Extracellular vesicles (EVs) play a crucial role in cell-to-cell communication and serve as source of biomarkers several pathologies. In this study, we aimed to characterize plasma-derived EVs isolated by ultracentrifugation (UC) or size exclusion chromatography (SEC) define the best method for proteomic functional studies. characterization included nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), detection western blotting, quantitative analysis. SEC-EVs samples had higher particle protein concentration, particle-to-protein ratio, smaller compared UC-EVs. A total 171 proteins were identified through Sequential Window Acquisition All Theoretical Mass Spectra (SWATH-MS) analysis, with 11 increased 5 The UC-EVs are complement immunoglobulins, while apolipoproteins present extracellular space. Functional studies from activated platelets confirmed that SEC exacerbate platelet aggregation, whereas there was no effect induced latter suggests obtained seem more suitable platelet-related those UC. results presented pave way future clinical orientated involving EVs.

Язык: Английский

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