Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-associated mutations

Translational Psychiatry, Год журнала: 2023, Номер 13(1)

Опубликована: Июль 6, 2023

Autism Spectrum Disorder (ASD) is characterized mainly by social and sensory-motor abnormal repetitive behavior patterns. Over hundreds of genes thousands genetic variants were reported to be highly penetrant causative ASD. Many these mutations cause comorbidities such as epilepsy intellectual disabilities (ID). In this study, we measured cortical neurons derived from induced pluripotent stem cells (iPSCs) patients with four in the GRIN2B, SHANK3, UBTF, well chromosomal duplication 7q11.23 region compared them a first-degree relative without mutation. Using whole-cell patch-clamp, observed that mutant demonstrated hyperexcitability early maturation control lines. These changes increased sodium currents, amplitude rate excitatory postsynaptic currents (EPSCs), more evoked action potentials response current stimulation early-stage cell development (3-5 weeks post differentiation). appeared all different lines, together previously data, indicate an may convergent phenotype ASD neurons.

Язык: Английский

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Synaptic dysfunction and extracellular matrix dysregulation in dopaminergic neurons from sporadic and E326K-GBA1 Parkinson’s disease patients

npj Parkinson s Disease, Год журнала: 2024, Номер 10(1)

Опубликована: Фев. 19, 2024

Parkinson's disease (PD) is a neurodegenerative with both genetic and sporadic origins. In this study, we investigated the electrophysiological properties, synaptic activity, gene expression differences in dopaminergic (DA) neurons derived from induced pluripotent stem cells (iPSCs) of healthy controls, PD (sPD) patients, patients E326K-GBA1 mutations. Our results demonstrate reduced sodium currents activity DA mutations, suggesting potential contribution to pathophysiology. We also observed distinct alterations sPD neurons, which included decrease currents. RNA sequencing analysis revealed unique dysregulated pathways further supporting notion that molecular mechanisms driving may differ between patients. agreement our previous reports, Extracellular matrix Focal adhesion were among top Overall, study confirms impaired convergent functional phenotype across multiple mutations as well sPD. At transcriptome level, find brain extracellular highly involved pathology PD-associated

Язык: Английский

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Differential gene expression patterns in Niemann-Pick Type C and Tay-Sachs diseases: Implications for neurodegenerative mechanisms

PLoS ONE, Год журнала: 2025, Номер 20(3), С. e0319401 - e0319401

Опубликована: Март 19, 2025

Lysosomal storage disorders (LSDs) are a group of rare genetic conditions characterized by the impaired function enzymes responsible for lipid digestion. Among these LSDs, Tay-Sachs disease (TSD) and Niemann-Pick type C (NPC) may share common gene expression profile. In this study, we conducted bioinformatics analysis to explore profile overlap between TSD NPC. Analyses were performed on RNA-seq datasets both NPC from Gene Expression Omnibus (GEO) database. Datasets subjected differential utilizing DESeq2 package in R programming language. A total 147 differentially expressed genes (DEG) found be shared datasets. Enrichment was then DEGs. We that DEGs predominantly associated with processes such as cell adhesion mediated integrin, cell-substrate adhesion, urogenital system development. Furthermore, construction protein-protein interaction (PPI) networks using Cytoscape software led identification four hub genes: APOE , CD44 SNCA ITGB5 . Those not only can unravel pathogenesis related neurologic diseases pathways, but also pave way towards targeted therapy LSDs.In addition, they serve potential biomarkers neurodegenerative warranting further investigations.

Язык: Английский

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Multifaceted collagen-DDR1 signaling in cancer

Trends in Cell Biology, Год журнала: 2023, Номер 34(5), С. 406 - 415

Опубликована: Сен. 12, 2023

Язык: Английский

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Gene Expression Profiling of Post Mortem Midbrain of Parkinson’s Disease Patients and Healthy Controls

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 707 - 707

Опубликована: Янв. 5, 2024

Parkinson's disease (PD) stands as the most prevalent degenerative movement disorder, marked by degeneration of dopaminergic neurons in substantia nigra midbrain. In this study, we conducted a transcriptome analysis utilizing post mortem mRNA extracted from both PD patients and healthy control (CTRL) individuals. Specifically, acquired eight samples individuals with six CTRL individuals, no discernible pathology detected latter group. RNA sequencing was using TapeStation 4200 system Agilent Technologies. A total 16,148 transcripts were identified, 92 mRNAs displaying differential expression between groups. 33 significantly up-regulated, while 59 down-regulated compared to controls. The identification statistically significant signaling pathways, an adjusted p-value threshold 0.05, unveiled noteworthy insights. enriched categories included cardiac muscle contraction (involving genes such ATPase Na+/K+ transporting subunit beta 2 (ATP1B2), solute carrier family 8 member A1 (SLC8A1), cytochrome c oxidase II (COX2)), GABAergic synapse GABA type receptor-associated protein-like 1 (GABARAPL1), G protein 5 (GNB5), 38 (SLC38A2), autophagy GABARAPL1 tumor p53-inducible nuclear (TP53INP2)), Fc gamma receptor (FcγR) mediated phagocytosis amphiphysin (AMPH)). These findings uncover new pathophysiological dimensions underlying PD, implicating associated heart contraction. This knowledge enhances diagnostic accuracy contributes advancement targeted therapies.

Язык: Английский

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Integrated bioinformatics analysis for exploring potential biomarkers related to Parkinson’s disease progression

BMC Medical Genomics, Год журнала: 2024, Номер 17(1)

Опубликована: Май 17, 2024

Abstract Background Parkinson’s disease (PD) is a progressive neurodegenerative with increasing prevalence. Effective diagnostic markers and therapeutic methods are still lacking. Exploring key molecular mechanisms for PD can help early diagnosis treatment improvement. Methods Three datasets GSE174052, GSE77668, GSE168496 were obtained from the GEO database to search differentially expressed circRNA (DECs), miRNAs (DEMis), mRNAs (DEMs). GO KEGG enrichment analyses, protein–protein interaction (PPI) network construction implemented explore possible actions of DEMs. Hub genes selected establish circRNA-related competing endogenous RNA (ceRNA) networks. Results There 1005 downregulated DECs, 21 upregulated DEMis, 266 234 DEMs identified. The significantly enriched in various PD-associated functions pathways such as extracellular matrix organization, dopamine synthesis, PI3K-Akt, calcium signaling pathways. Twenty-one hub screened out, PD-related ceRNA regulatory was constructed containing 31 circRNAs, one miRNA (miR-371a-3p), gene ( KCNJ6 ). Conclusion We identified networks, providing new directions treatment.

Язык: Английский

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Multi-omics insights into bone tissue injury and healing: bridging Orthopedic trauma and regenerative medicine

Burns & Trauma, Год журнала: 2025, Номер 13

Опубликована: Янв. 1, 2025

Abstract To preserve functionality, bone is an active tissue that can constantly reconstruct itself through modeling and remodeling. It plays critical roles in the body, including maintaining mineral homeostasis, serving as adult human body’s core site of hematopoiesis, supporting structures soft tissues. possesses natural regeneration capacity, but large complex lesions often require surgical intervention. Multiple omics integrate proteomics, metabolomics, genomics, transcriptomics to provide a comprehensive understanding biological processes like injury healing engineering. Recently, engineering regenerative medicines have offered promising tools for using multi-omics approach. Thus, this article will highlight role multiple healing. discuss developing substitutes replace translational medicine. Lastly, new developments medicine, along with approaches, offer regeneration.

Язык: Английский

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Construction of epilepsy diagnosis model based on cell senescence-related genes and its potential mechanism

Frontiers in Neurology, Год журнала: 2025, Номер 16

Опубликована: Май 30, 2025

Introduction Epilepsy is a chronic brain disease with certain degree of neurodegeneration and caused by abnormal discharges neurons. The mechanism cell senescence has garnered increasing attention in neurodegenerative diseases. However, the role onset progression epilepsy unclear. Therefore, this study constructed diagnostic model based on cellular senescence-related genes (CSRGs) to analyze their pathogenesis. Methods differentially expressed (DEGs) were screened from epileptic sample dataset gene expression omnibus (GEO) database, DEGs (CSRDEGs) related identified CSRGs crossover. functional enrichment characteristics CSRDEGs analyzed using ontology (GO) Kyoto encyclopedia genomes (KEGG) analyses. differences biological processes between high low-risk groups set analysis (GSEA). For construction, logistic regression, random forest, least absolute shrinkage selection operator (LASSO) regression employed identify key genes, including ribosomal protein S6 kinase alpha-3 (RPS6KA3), cathepsin D (CTSD), zinc finger 101 (ZNF101). Subsequently, multifactor was developed evaluate risk these genes. Results exhibited higher area under curve (AUC) values GSE data sets 143272 32534, producing encouraging results. Finally, mRNA-miRNA mRNA-transcription factors (TFs) networks revealed potential regulatory selected critical disease. Discussion This elucidated possible process diseases through bioinformatics analysis, offering target for personalized diagnosis precise treatment.

Язык: Английский

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A Systematic Review of Extracellular Matrix-Related Alterations in Parkinson’s Disease

Brain Sciences, Год журнала: 2024, Номер 14(6), С. 522 - 522

Опубликована: Май 21, 2024

The role of the extracellular matrix (ECM) in Parkinson's disease (PD) is not well understood, even though it critical for neuronal structure and signaling. This systematic review identified top deregulated ECM-related pathways studies that used gene set enrichment analyses (GSEA) to document transcriptomic, proteomic, or genomic alterations PD. PubMed Google scholar were searched transcriptomics, proteomics, genomics employed GSEA on data from PD tissues cells reported among top-10 most enriched versus controls. Twenty-seven included, two which multiple omics analyses. Transcriptomics proteomics conducted a variety tissue cell types. Of 17 transcriptomics (16 sets), 13 one more adhesion sets pathways, primarily related focal adhesion. Among 8 studies, 5 altered overarching ECM 10. 4 3 findings summarized here suggest organization/structure (particularly adhesion) are should be focus future studies.

Язык: Английский

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Case Report: A Case of a Patient with Smith–Magenis Syndrome and Early-Onset Parkinson’s Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8447 - 8447

Опубликована: Авг. 2, 2024

Smith-Magenis Syndrome (SMS) is a rare genetic disorder, characterized by intellectual disability (ID), behavioral impairments, and sleep disturbances, as well multiple organ anomalies in some affected individuals. The syndrome caused deletion the chromosome band around 17p11.2, including Retinoic Acid Induced 1 (

Язык: Английский

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