ArticleCellular and molecular life sciences : CMLS2017
Synthetic alpha-synuclein fibrils cause mitochondrial impairment and selective dopamine neurodegeneration in part via iNOS-mediated nitric oxide production.
Article in Cellular and molecular life sciences : CMLS, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Targeting TREM2 for Parkinson's Disease: Where to Go?Frontiers in immunology · 2021Pooled it
- The A53T Parkinson's Disease Mouse Model Shows Abnormal Outer Retinal OCT Metabolic Biomarker Patterns.Investigative ophthalmology & visual science · 2026Article
- Mitochondrial transplantation reverses the senescence phenotype of SH-SY5Y cells.Molecular therapy. Advances · 2026Article
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Reduced microvascular coverage links a hypoxia-associated niche to microglial autophagic dysfunction in Parkinson's disease.Acta neuropathologica communications · 2026Article
- Alpha-synuclein at the crossroads of host-virus interactions: immunological roles beyond the nervous system.Journal of virology · 2026Review
- In vitro and in vivo rescue of dopaminergic neurons in Parkinson's disease models after Parkin gene therapy.Gene therapy · 2026Article
- Cell-based regenerative interventions in Parkinson's disease: Overcoming pharmacological limitations.Acta pharmaceutica Sinica. B · 2026Review
- Mitochondrial DNA: a molecular switch driving sterile neuroinflammation.Translational neurodegeneration · 2026Review
- Direct current stimulation induced reduction in α-synuclein in primary neurons: targeting Parkinson's disease.Brain communications · 2026Article
- Neuroprotective Attributes of Gut-derived Urolithins in Parkinson's Disease.Molecular neurobiology · 2025Review
- Potential Therapeutic Effects of Astragaloside IV in Parkinson's Disease Models via Modulation of α-syn-γH2AX-STING-IFN-I Axis.Molecular neurobiology · 2025Article
- The development and emerging trends in Parkinson's disease from the perspective of mitochondrial dysfunction: a bibliometric analysis using CiteSpace.Journal of neurology · 2025Review
- Hypoxia ameliorates neurodegeneration and movement disorder in a mouse model of Parkinson's disease.Nature neuroscience · 2025Article
- Role of mitochondria in physiological activities, diseases, and therapy.Molecular biomedicine · 2025Review
- Application of Network Pharmacology in the Treatment of Neurodegenerative Diseases with Traditional Chinese Medicine.Planta medica · 2025Review
- Female mice exhibit resistance to disease progression despite early pathology in a transgenic mouse model inoculated with alpha-synuclein fibrils.Communications biology · 2025Article
- Review
- Gut-brain axis modulation in remote rehabilitation of Parkinson's disease: reconstructing the fecal metabolome and nigral network connectivity.Frontiers in neurology · 2025Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Intracellular accumulation of α-synuclein (α-syn) are hallmarks of synucleinopathies, including Parkinson's disease (PD). Exogenous addition of preformed α-syn fibrils (PFFs) into primary hippocampal neurons induced α-syn aggregation and accumulation. Likewise, intrastriatal inoculation of PFFs into mice and non-human primates generates Lewy bodies and Lewy neurites associated with PD-like neurodegeneration. Herein, we investigate the putative effects of synthetic human PFFs on cultured rat ventral midbrain dopamine (DA) neurons. A time- and dose-dependent accumulation of α-syn was observed following PFFs exposure that also underwent phosphorylation at serine 129. PFFs treatment decreased the expression levels of synaptic proteins, caused alterations in axonal transport-related proteins, and increased H2AX Ser139 phosphorylation. Mitochondrial impairment (including modulation of mitochondrial dynamics-associated protein content), enhanced oxidative stress, and an inflammatory response were also detected in our experimental paradigm. In attempt to unravel a potential molecular mechanism of PFFs neurotoxicity, the expression of inducible nitric oxide synthase was blocked; a significant decline in protein nitration levels and protection against PFFs-induced DA neuron death were observed. Combined exposure to PFFs and rotenone resulted in an additive toxicity. Strikingly, many of the harmful effects found were more prominent in DA rather than non-DA neurons, suggestive of higher susceptibility to degenerate. These findings provide new insights into the role of α-syn in the pathogenesis of PD and could represent a novel and valuable model to study DA-related neurodegeneration.
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