ArticleNeurobiology of disease2015
PARK2 patient neuroprogenitors show increased mitochondrial sensitivity to copper.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 49 citations in OpenAlex.
- Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson's Disease Pathogenesis.Aging and disease · 2024Review
- Mitochondrial pathways of copper neurotoxicity: focus on mitochondrial dynamics and mitophagy.Frontiers in molecular neuroscience · 2024Review
- Overexpression of Parkin in the Neuronal Progenitor Cells from a Patient with Parkinson's Disease Shifts the Transcriptome Towards the Normal State.Molecular neurobiology · 2023Article
- Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson's Disease.Genes · 2022Review
- Genomic, transcriptomic, and metabolomic profiles of hiPSC-derived dopamine neurons from clinically discordant brothers with identical PRKN deletions.NPJ Parkinson's disease · 2022Article
- A cuproptosis and copper metabolism-related gene prognostic index for head and neck squamous cell carcinoma.Frontiers in oncology · 2022Article
- Mitochondrial Phenotypes in Parkinson's Diseases-A Focus on Human iPSC-Derived Dopaminergic Neurons.Cells · 2021Review
- Parkin, an E3 Ubiquitin Ligase, Plays an Essential Role in Mitochondrial Quality Control in Parkinson's Disease.Cellular and molecular neurobiology · 2021Review
- A bistable, multiport valve enables microformulators creating microclinical analyzers that reveal aberrant glutamate metabolism in astrocytes derived from a tuberous sclerosis patient.Sensors and actuators. B, Chemical · 2021Article
- The Impact of Environmental Factors on Monogenic Mendelian Diseases.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- MicroRNAs Regulating Autophagy in Neurodegeneration.Advances in experimental medicine and biology · 2021Article
- Role of 5-Hydroxytryptamine and Intestinal Flora on Depressive-Like Behavior Induced by Lead Exposure in Rats.BioMed research international · 2021Article
- Patient-Derived Induced Pluripotent Stem Cell-Based Models in Parkinson's Disease for Drug Identification.International journal of molecular sciences · 2020Review
- Using induced pluripotent stem cell neuronal models to study neurodegenerative diseases.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Genetic predispositions of Parkinson's disease revealed in patient-derived brain cells.NPJ Parkinson's disease · 2020Review
- A compendious summary of Parkinson's disease patient-derived iPSCs in the first decade.Annals of translational medicine · 2019Review
- Trafficking mechanisms of P-type ATPase copper transporters.Current opinion in cell biology · 2019Review
- Manganese-Induced Neurotoxicity: New Insights Into the Triad of Protein Misfolding, Mitochondrial Impairment, and Neuroinflammation.Frontiers in neuroscience · 2019Review
- Modeling Cell-Cell Interactions in Parkinson's Disease Using Human Stem Cell-Based Models.Frontiers in cellular neuroscience · 2019Article
- The Endolysosomal System and Proteostasis: From Development to Degeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Poorly-defined interactions between environmental and genetic risk factors underlie Parkinson's disease (PD) etiology. Here we tested the hypothesis that human stem cell derived forebrain neuroprogenitors from patients with known familial risk for early onset PD will exhibit enhanced sensitivity to PD environmental risk factors compared to healthy control subjects without a family history of PD. Two male siblings (SM and PM) with biallelic loss-of-function mutations in PARK2 were identified. Human induced pluripotent stem cells (hiPSCs) from SM, PM, and four control subjects with no known family histories of PD or related neurodegenerative diseases were utilized. We tested the hypothesis that hiPSC-derived neuroprogenitors from patients with PARK2 mutations would show heightened cell death, mitochondrial dysfunction, and reactive oxygen species generation compared to control cells as a result of exposure to heavy metals (PD environmental risk factors). We report that PARK2 mutant neuroprogenitors showed increased cytotoxicity with copper (Cu) and cadmium (Cd) exposure but not manganese (Mn) or methyl mercury (MeHg) relative to control neuroprogenitors. PARK2 mutant neuroprogenitors also showed a substantial increase in mitochondrial fragmentation, initial ROS generation, and loss of mitochondrial membrane potential following Cu exposure. Our data substantiate Cu exposure as an environmental risk factor for PD. Furthermore, we report a shift in the lowest observable effect level (LOEL) for greater sensitivity to Cu-dependent mitochondrial dysfunction in patients SM and PM relative to controls, correlating with their increased genetic risk for PD.
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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.