ArticleCell death & disease2015
Elevated α-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson's patient-derived induced pluripotent stem cells.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Early Signs of Molecular Defects in iPSC-Derived Neural Stems Cells from Patients with Familial Parkinson's Disease.Biomolecules · 2022Pooled it
- Atorvastatin Shows Limited Disease-Modifying Effects in an A53T α-Synuclein Mouse Model of Parkinson's Disease.Neurotoxicity research · 2026Article
- Lysosome-Acidifying Nanoparticles Rescue A30P α-Synuclein Induced Neuronal Death in Cellular and Drosophila Models of Parkinson's Disease.Advanced healthcare materials · 2026Article
- Foldamers rescue synucleinopathy phenotypes in multiple in vitro and in vivo models.Science translational medicine · 2026Article
- Autophagy dysfunction in iPSCs-derived neurons and midbrain organoids carrying a SNCA triplication.NPJ Parkinson's disease · 2026Article
- Copper Dyshomeostasis Affects α-Synuclein Clearance Mechanisms in Parkinson's Disease: Insights from In Vitro Models and Translational Evidence.International journal of molecular sciences · 2026Review
- SNCA triplication disrupts proteostasis and extracellular architecture prior to neurodegeneration in human midbrain organoids.NPJ Parkinson's disease · 2026Article
- Bioenergetic and protein processing imbalances in iPSC-dopamine neurons from individuals with idiopathic Parkinson's disease.Neurobiology of disease · 2026Article
- Mutations in the Key Autophagy Tethering Factor EPG5 Link Neurodevelopmental and Neurodegenerative Disorders Including Early-Onset Parkinsonism.Annals of neurology · 2025Article
- Morphological profiling reveals neuroprotection via mitochondrial uncoupling in human dopaminergic neurons.Scientific reports · 2025Article
- Dopamine and cortical neurons with different Parkinsonian mutations show variation in lysosomal and mitochondrial dysfunction.NPJ Parkinson's disease · 2025Article
- Vimentin network dysregulation mediates neurite deficits inScience advances · 2025Article
- Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.The Journal of cell biology · 2025Review
- E46K α-Synuclein Mutation Fails to Promote Neurite Outgrowth by Not Inducing Cdc42EP2 Expression, Unlike Wild-Type or A53T α-Synuclein in SK-N-SH Cells.Brain sciences · 2024Article
- Astrocytes contribute to toll-like receptor 2-mediated neurodegeneration and alpha-synuclein pathology in a human midbrain Parkinson's model.Translational neurodegeneration · 2024Article
- Alpha-Synuclein Gene Alterations Modulate Tyrosine Hydroxylase in Human iPSC-Derived Neurons in a Parkinson's Disease Animal Model.Life (Basel, Switzerland) · 2024Article
- Human α-synuclein overexpression upregulates SKOR1 in a rat model of simulated nigrostriatal ageing.Aging cell · 2024Article
- Nonintuitive Immunogenicity and Plasticity of Alpha-Synuclein Conformers: A Paradigm for Smart Delivery of Neuro-Immunotherapeutics.Pharmaceutics · 2024Review
- The Role of Structural Variants in the Genetic Architecture of Parkinson's Disease.International journal of molecular sciences · 2024Review
- Thrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson's disease.Cell death discovery · 2024Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have assessed the impact of α-synuclein overexpression on the differentiation potential and phenotypic signatures of two neural-committed induced pluripotent stem cell lines derived from a Parkinson's disease patient with a triplication of the human SNCA genomic locus. In parallel, comparative studies were performed on two control lines derived from healthy individuals and lines generated from the patient iPS-derived neuroprogenitor lines infected with a lentivirus incorporating a small hairpin RNA to knock down the SNCA mRNA. The SNCA triplication lines exhibited a reduced capacity to differentiate into dopaminergic or GABAergic neurons and decreased neurite outgrowth and lower neuronal activity compared with control cultures. This delayed maturation phenotype was confirmed by gene expression profiling, which revealed a significant reduction in mRNA for genes implicated in neuronal differentiation such as delta-like homolog 1 (DLK1), gamma-aminobutyric acid type B receptor subunit 2 (GABABR2), nuclear receptor related 1 protein (NURR1), G-protein-regulated inward-rectifier potassium channel 2 (GIRK-2) and tyrosine hydroxylase (TH). The differentiated patient cells also demonstrated increased autophagic flux when stressed with chloroquine. We conclude that a two-fold overexpression of α-synuclein caused by a triplication of the SNCA gene is sufficient to impair the differentiation of neuronal progenitor cells, a finding with implications for adult neurogenesis and Parkinson's disease progression, particularly in the context of bioenergetic dysfunction.
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