ArticleNPJ Parkinson's disease2024
Synaptic dysfunction and extracellular matrix dysregulation in dopaminergic neurons from sporadic and E326K-GBA1 Parkinson's disease patients.
Article in NPJ Parkinson's disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Modulation of the TGF-β/Smad Signaling Pathway by a Bioactive Oxidized Polygonati Rhizoma Polysaccharide Crosslinked Chitosan Hydrogel as Therapeutic Carrier for Parkinson's Disease Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dysregulation of the Extracellular Matrix in the Synaptic Pathology of Parkinson's Disease: Molecular Mechanisms and Novel Therapeutic Approaches.Life (Basel, Switzerland) · 2026Review
- The epitranscriptomic m6A RNA modification modulates the synapse in ageing and in a mouse model of synucleinopathy.NPJ Parkinson's disease · 2026Article
- Transcriptional dysregulation in the cerebellum triggered by oligodendroglial α-synucleinopathy: insights from a transgenic mouse into the early disease mechanisms of MSA.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Review
- New insights into synaptic vesicle dysfunction in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Extracellular vesicles from stem cells rescue cellular phenotypes and behavioral deficits in SHANK3-associated ASD neuronal and mouse models.Cell death & disease · 2026Article
- SNCA triplication disrupts proteostasis and extracellular architecture prior to neurodegeneration in human midbrain organoids.NPJ Parkinson's disease · 2026Article
- HUWE1 regulates mitophagy to protect dopaminergic neurons from 6-OHDA- and MPP⁺-induced neurotoxicity.Cell biology and toxicology · 2026Article
- Multi-omics insights into GBA1-associated Parkinson's disease: interplay of genomics, transcriptomics, proteomics, and lipidomics.Molecular neurodegeneration · 2026Review
- Developmental perfluorooctane sulfonate (PFOS) exposure alters gene expression in nucleus accumbens and prefrontal cortex and impairs cognition in rats: A transcriptomic and mediation analysis.Ecotoxicology and environmental safety · 2026Article
- Extracellular Matrix Remodeling in Motor Neuron Diseases.International journal of molecular sciences · 2025Review
- The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections.The American journal of pathology · 2025Review
- Epigenomic profile of GBA1 in Parkinson's disease.Parkinsonism & related disorders · 2025Article
- From Genome-Wide SNPs to Neuroimmune Crosstalk: Mapping the Genetic Landscape of IBD and Its Brain Overlap.Biology · 2025Article
- Stable Dopamine-Signaling mRNA Co-Expression in the Substantia Nigra Is Deregulated in Pathological Conditions, but Not in Dopamine Transporter Knockout Rats.Biomolecules · 2025Article
- Article
- Amyotrophic Lateral Sclerosis and Parkinson's Disease: Brain Tissue Transcriptome Analysis Reveals Interactions.Molecular neurobiology · 2025Review
- Nanosensor-based imaging of realtime dopamine release in neurons derived from iPSCs of patients with Parkinson's disease.Materials today. Bio · 2025Article
- Intracellular α-synuclein assemblies are sufficient to alter nanoscale diffusion in the striatal extracellular space.NPJ Parkinson's disease · 2024Article
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
Parkinson's disease (PD) is a neurodegenerative disease with both genetic and sporadic origins. In this study, we investigated the electrophysiological properties, synaptic activity, and gene expression differences in dopaminergic (DA) neurons derived from induced pluripotent stem cells (iPSCs) of healthy controls, sporadic PD (sPD) patients, and PD patients with E326K-GBA1 mutations. Our results demonstrate reduced sodium currents and synaptic activity in DA neurons derived from PD patients with E326K-GBA1 mutations, suggesting a potential contribution to PD pathophysiology. We also observed distinct electrophysiological alterations in sPD DA neurons, which included a decrease in synaptic currents. RNA sequencing analysis revealed unique dysregulated pathways in sPD neurons and E326K-GBA1 neurons, further supporting the notion that molecular mechanisms driving PD may differ between PD patients. In agreement with our previous reports, Extracellular matrix and Focal adhesion pathways were among the top dysregulated pathways in DA neurons from sPD patients and from patients with E326K-GBA1 mutations. Overall, our study further confirms that impaired synaptic activity is a convergent functional phenotype in DA neurons derived from PD patients across multiple genetic mutations as well as sPD. At the transcriptome level, we find that the brain extracellular matrix is highly involved in PD pathology across multiple PD-associated mutations as well as sPD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.