ArticleHuman molecular genetics2019
Multiplication of the SNCA locus exacerbates neuronal nuclear aging.
Article in Human molecular genetics, 2019. 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, 30 citations in OpenAlex.
- Single cell transcriptomics reveals enrichment of aggregation-prone alpha-synuclein isoforms across synucleinopathies.bioRxiv : the preprint server for biology · 2025Article
- Nuclear pore and nucleocytoplasmic transport impairment in oxidative stress-induced neurodegeneration: relevance to molecular mechanisms in Pathogenesis of Parkinson's and other related neurodegenerative diseases.Molecular neurodegeneration · 2024Review
- Single-nucleus multi-omics of Parkinson's disease reveals a glutamatergic neuronal subtype susceptible to gene dysregulation via alteration of transcriptional networks.Acta neuropathologica communications · 2024Article
- Neuronal-type-specific epigenome editing to decreaseMolecular therapy. Nucleic acids · 2024Article
- Human-Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons and Glia for the Elucidation of Pathogenic Mechanisms in Alzheimer's Disease.Methods in molecular biology (Clifton, N.J.) · 2023Review
- DNA Methylation Signature of Aging: Potential Impact on the Pathogenesis of Parkinson's Disease.Journal of Parkinson's disease · 2023Review
- Cellular Models of Alpha-Synuclein Aggregation: What Have We Learned and Implications for Future Study.Biomedicines · 2022Review
- Passage number affects differentiation of sensory neurons from human induced pluripotent stem cells.Scientific reports · 2022Article
- Glycoconjugate journal special issue on: the glycobiology of Parkinson's disease.Glycoconjugate journal · 2022Review
- Patient-Specific iPSCs-Based Models of Neurodegenerative Diseases: Focus on Aberrant Calcium Signaling.International journal of molecular sciences · 2022Review
- Ferroptosis Related Genes in Ischemic and Idiopathic Cardiomyopathy: Screening for Potential Pharmacological Targets.Frontiers in cell and developmental biology · 2022Article
- Article
- α-synuclein pathogenesis in hiPSC models of Parkinson's disease.Neuronal signaling · 2021Review
- Modelling Parkinson's Disease: iPSCs towards Better Understanding of Human Pathology.Brain sciences · 2021Review
- The Path to Progress Preclinical Studies of Age-Related Neurodegenerative Diseases: A Perspective on Rodent and hiPSC-Derived Models.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Targeting α-Synuclein in Parkinson's Disease by Induced Pluripotent Stem Cell Models.Frontiers in neurology · 2021Review
- The application of in vitro-derived human neurons in neurodegenerative disease modeling.Journal of neuroscience research · 2021Review
- The mechanistic role of alpha-synuclein in the nucleus: impaired nuclear function caused by familial Parkinson's disease SNCA mutations.Human molecular genetics · 2020Article
- Modeling Parkinson's Disease Using Induced Pluripotent Stem Cells.Stem cells international · 2020Review
- Cellular models of alpha-synuclein toxicity and aggregation.Journal of neurochemistry · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Human-induced Pluripotent Stem Cell (hiPSC)-derived models have advanced the study of neurodegenerative diseases, including Parkinson's disease (PD). While age is the strongest risk factor for these disorders, hiPSC-derived models represent rejuvenated neurons. We developed hiPSC-derived Aged dopaminergic and cholinergic neurons to model PD and related synucleinopathies. Our new method induces aging through a `semi-natural' process, by passaging multiple times at the Neural Precursor Cell stage, prior to final differentiation. Characterization of isogenic hiPSC-derived neurons using heterochromatin and nuclear envelope markers, as well as DNA damage and global DNA methylation, validated our age-inducing method. Next, we compared neurons derived from a patient with SNCA-triplication (SNCA-Tri) and a Control. The SNCA-Tri neurons displayed exacerbated nuclear aging, showing advanced aging signatures already at the Juvenile stage. Noteworthy, the Aged SNCA-Tri neurons showed more α-synuclein aggregates per cell versus the Juvenile. We suggest a link between the effects of aging and SNCA overexpression on neuronal nuclear architecture.
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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.