ArticleCell death & disease2019
Mitochondrial damage by α-synuclein causes cell death in human dopaminergic neurons.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 181 citations in OpenAlex.
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- Large-scale bidirectional arrayed genetic screens identify OXR1 and EMC4 as modifiers of αSynuclein aggregation.FEBS open bio · 2026Article
- Integrated Multi-Endpoint Analysis of Soluble Copper(II) Chloride-Induced Oxidative Stress, Mitochondrial Dysfunction, and Genotoxicity in RAW264.7 Macrophages.Biological trace element research · 2026Article
- Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies.Molecular systems biology · 2026Article
- PINK1/Parkin-dependent mitophagy mediates astrocytic inflammatory responses to mitochondrial damage.bioRxiv : the preprint server for biology · 2026Article
- Engineered Exosomes: Innovative Strategies for Precision Drug Delivery in Parkinson's Disease.Molecular neurobiology · 2026Review
- Stem Cell-Derived Exosomes Regulate Mitochondrial Function: A Novel Strategy for Parkinson's Disease Therapy.Molecular neurobiology · 2026Review
- Silicon quantum dots for neurotheranostic applications in dopamine detection.Journal of nanobiotechnology · 2026Review
- Incense Aerosol-Induced Neurotoxicity Disrupts α-Synuclein Homeostasis in a Cellular Parkinson's Disease Model, Distinct from Cigarette Aerosols.Chemical research in toxicology · 2026Article
- APurinergic signalling · 2026Article
- Systematic evaluation of mitochondrial morphology regulators for amelioration of neuronal α-synucleinopathy.NPJ Parkinson's disease · 2026Article
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- Ultrastructural perspectives on the enteric nervous system in Parkinson's disease.Frontiers in neuroscience · 2026Review
- Multifunctional nanozyme platforms in central nervous system therapies: from rational design to translational medicine.Theranostics · 2026Review
- Ferroptosis inhibition protects against α-synuclein-related neuronal cell death.Cell death & disease · 2025Article
- Bridging the gap in Parkinson's disease research: from general pathophysiology to advanced 3d cell culture models.Cell communication and signaling : CCS · 2025Review
- Regulation of mitochondrial dynamics and function by melatonin type 1 receptor in parkinson's disease.Cellular and molecular life sciences : CMLS · 2025Article
- Aggregation and Propagation of α-Synuclein in Parkinson's Disease: A Bibliometric Perspective.Brain and behavior · 2025Article
- Current Understanding of Protein Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Molecular mechanisms of α-syn abnormal phase separation in cognitive impairment induced by chronic intermittent hypoxia and the neuroprotective effects of Danshensu methyl ester.Molecular medicine (Cambridge, Mass.) · 2025Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evolving concepts on Parkinson's disease (PD) pathology suggest that α-synuclein (aSYN) promote dopaminergic neuron dysfunction and death through accumulating in the mitochondria. However, the consequence of mitochondrial aSYN localisation on mitochondrial structure and bioenergetic functions in neuronal cells are poorly understood. Therefore, we investigated deleterious effects of mitochondria-targeted aSYN in differentiated human dopaminergic neurons in comparison with wild-type (WT) aSYN overexpression and corresponding EGFP (enhanced green fluorescent protein)-expressing controls. Mitochondria-targeted aSYN enhanced mitochondrial reactive oxygen species (ROS) formation, reduced ATP levels and showed severely disrupted structure and function of the dendritic neural network, preceding neuronal death. Transmission electron microscopy illustrated distorted cristae and many fragmented mitochondria in response to WT-aSYN overexpression, and a complete loss of cristae structure and massively swollen mitochondria in neurons expressing mitochondria-targeted aSYN. Further, the analysis of mitochondrial bioenergetics in differentiated dopaminergic neurons, expressing WT or mitochondria-targeted aSYN, elicited a pronounced impairment of mitochondrial respiration. In a pharmacological compound screening, we found that the pan-caspase inhibitors QVD and zVAD-FMK, and a specific caspase-1 inhibitor significantly prevented aSYN-induced cell death. In addition, the caspase inhibitor QVD preserved mitochondrial function and neuronal network activity in the human dopaminergic neurons overexpressing aSYN. Overall, our findings indicated therapeutic effects by caspase-1 inhibition despite aSYN-mediated alterations in mitochondrial morphology and function.
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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.