ArticleFrontiers in aging neuroscience2021
Exogenous Alpha-Synuclein Evoked Parkin Downregulation Promotes Mitochondrial Dysfunction in Neuronal Cells. Implications for Parkinson's Disease Pathology.
Article in Frontiers in aging neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- The underlying mechanism of physical exercise on neurodegenerative diseases: the mediating role of psychological stress and resilience: a systematic review.Frontiers in psychology · 2025Pooled it
- SUMOylation in Mitochondrial Quality Control: Mechanisms and Implications for Neurodegenerative Disease.Molecular neurobiology · 2026Review
- Soluble α-synuclein oligomers drive transient corticostriatal pathology and delayed nigral vulnerability in a mouse model of early α-synucleinopathy.Acta neuropathologica communications · 2026Article
- Zebrafish Models of Parkinson's Disease: From Pathogenesis to Drug Discovery.International journal of molecular sciences · 2026Review
- Toxic Alpha-Synuclein and the Opening of the Gate: Blood-Brain Barrier Damage and Stepwise Leukocyte Infiltration.Cellular and molecular neurobiology · 2026Review
- α-Synuclein oligomers slow down action potential firing and enhance dopamine release by increasing Cav2.2 currents in midbrain dopaminergic neurons.The Journal of physiology · 2026Article
- Inhibition of de novo ceramide synthesis mitigates alpha-synuclein pathology in a Parkinson's disease mouse model.NPJ Parkinson's disease · 2026Article
- Cardiolipin and mitochondrial membrane integrity in neurodegeneration: insights from α-synuclein-driven Parkinson's disease.Acta neuropathologica communications · 2025Review
- Neuroprotective Parkinson's Disease Therapeutic: Transition Metal Dichalcogenide Nanoflower Treatments Alleviate Pathological Cell Stress.bioRxiv : the preprint server for biology · 2025Article
- Review
- Mitochondrial Quality Control in Neurodegeneration and Cancer: A Common Denominator, Distinct Therapeutic Challenges.International journal of molecular sciences · 2025Review
- New insights into pathogenisis and therapies of P2X7R in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- TFE3-mediated neuroprotection: Clearance of aggregated α-synuclein and accumulated mitochondria in the AAV-α-synuclein model of Parkinson's disease.Genes & diseases · 2025Article
- Zebrafish-Based Parkinson's Disease Models: Unveiling Genetic Mechanisms and Therapeutic Pathways.CNS & neurological disorders drug targets · 2025Review
- The interplay between α-synuclein aggregation and necroptosis in Parkinson's disease: a spatiotemporal perspective.Frontiers in neuroscience · 2025Review
- Review
- The role of neuron-like cell lines and primary neuron cell models in unraveling the complexity of neurodegenerative diseases: a comprehensive review.Molecular biology reports · 2024Review
- Thioredoxin-1 decreases alpha-synuclein induced by MPTP through promoting autophagy-lysosome pathway.Cell death discovery · 2024Article
- Novel Insights into Parkin-Mediated Mitochondrial Dysfunction and "Mito-Inflammation" in α-Synuclein Toxicity. The Role of the cGAS-STING Signalling Pathway.Journal of inflammation research · 2024Review
- Liquid-liquid phase separation and conformational strains ofFrontiers in molecular neuroscience · 2024Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant secretion and accumulation of α-synuclein (α-Syn) as well as the loss of parkin function are associated with the pathogenesis of Parkinson's disease (PD). Our previous study suggested a functional interaction between those two proteins, showing that the extracellular α-Syn evoked post-translational modifications of parkin, leading to its autoubiquitination and degradation. While parkin plays an important role in mitochondrial biogenesis and turnover, including mitochondrial fission/fusion as well as mitophagy, the involvement of parkin deregulation in α-Syn-induced mitochondrial damage is largely unknown. In the present study, we demonstrated that treatment with exogenous α-Syn triggers mitochondrial dysfunction, reflected by the depolarization of the mitochondrial membrane, elevated synthesis of the mitochondrial superoxide anion, and a decrease in cellular ATP level. At the same time, we observed a protective effect of parkin overexpression on α-Syn-induced mitochondrial dysfunction. α-Syn-dependent disturbances of mitophagy were also shown to be directly related to reduced parkin levels in mitochondria and decreased ubiquitination of mitochondrial proteins. Also, α-Syn impaired mitochondrial biosynthesis due to the parkin-dependent reduction of PGC-1α protein levels. Finally, loss of parkin function as a result of α-Syn treatment induced an overall breakdown of mitochondrial homeostasis that led to the accumulation of abnormal mitochondria. These findings may thus provide the first compelling evidence for the direct association of α-Syn-mediated parkin depletion to impaired mitochondrial function in PD. We suggest that improvement of parkin function may serve as a novel therapeutic strategy to prevent mitochondrial impairment and neurodegeneration in PD (thereby slowing the progression of the disease).
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