ArticleNeurobiology of aging2018
Intercellular transfer of pathogenic α-synuclein by extracellular vesicles is induced by the lipid peroxidation product 4-hydroxynonenal.
Article in Neurobiology of aging, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Potential Exosome Biomarkers for Parkinson's Disease Diagnosis: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- A systematic review of molecular approaches that link mitochondrial dysfunction and neuroinflammation in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Pooled it
- Mechanisms of Brain Aging and Their Links to Alzheimer's and Parkinson's Disease Pathology.International journal of molecular sciences · 2026Review
- Clinical Validation of α-Synuclein in Salivary Extracellular Vesicles as a Biomarker for Parkinson's Disease: A Longitudinal Study.European journal of neurology · 2026Article
- Lipid metabolism in health and disease: Mechanistic and therapeutic insights for Parkinson's disease.Chinese medical journal · 2025Review
- α-Synuclein Pathology Spreads in a Midbrain-Hindbrain Assembloid Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oxidative Stress-mediated Lipid Peroxidation-derived Lipid Aldehydes in the Pathophysiology of Neurodegenerative Diseases.Current neuropharmacology · 2025Review
- Extraction of redox extracellular vesicles using exclusion-based sample preparation.Analytical and bioanalytical chemistry · 2024Article
- Exosome is a Fancy Mobile Sower of Ferroptosis.Journal of cardiovascular translational research · 2024Review
- Extracellular Vesicles as Biomarkers for Parkinson's Disease: How Far from Clinical Translation?International journal of molecular sciences · 2024Review
- Advancements in Genetic and Biochemical Insights: Unraveling the Etiopathogenesis of Neurodegeneration in Parkinson's Disease.Biomolecules · 2024Review
- Targeting ferroptosis with the lipoxygenase inhibitor PTC-041 as a therapeutic strategy for the treatment of Parkinson's disease.PloS one · 2024Article
- Alpha Synuclein: Neurodegeneration and Inflammation.International journal of molecular sciences · 2023Review
- Propagation of Parkinson's disease by extracellular vesicle production and secretion.Biochemical Society transactions · 2022Review
- Review
- Cellular Models of Alpha-Synuclein Aggregation: What Have We Learned and Implications for Future Study.Biomedicines · 2022Review
- Exosomes in Alpha-Synucleinopathies: Propagators of Pathology or Potential Candidates for Nanotherapeutics?Biomolecules · 2022Review
- Extracellular vesicles released after cranial radiation: An insight into an early mechanism of brain injury.Brain research · 2022Article
- Review
- Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson's disease.NPJ Parkinson's disease · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Parkinson's disease (PD) is characterized by accumulations of toxic α-synuclein aggregates in vulnerable neuronal populations in the brainstem, midbrain, and cerebral cortex. Recent findings suggest that α-synuclein pathology can be propagated transneuronally, but the underlying molecular mechanisms are unknown. Advances in the genetics of rare early-onset familial PD indicate that increased production and/or reduced autophagic clearance of α-synuclein can cause PD. The cause of the most common late-onset PD is unclear, but may involve metabolic compromise and oxidative stress upstream of α-synuclein accumulation. As evidence, the lipid peroxidation product 4-hydroxynonenal (HNE) is elevated in the brain during normal aging and moreso in brain regions afflicted with α-synuclein pathology. Here, we report that HNE increases aggregation of endogenous α-synuclein in primary neurons and triggers the secretion of extracellular vesicles (EVs) containing cytotoxic oligomeric α-synuclein species. EVs released from HNE-treated neurons are internalized by healthy neurons which as a consequence degenerate. Levels of endogenously generated HNE are elevated in cultured cells overexpressing human α-synuclein, and EVs released from those cells are toxic to neurons. The EV-associated α-synuclein is located both inside the vesicles and on their surface, where it plays a role in EV internalization by neurons. On internalization, EVs harboring pathogenic α-synuclein are transported both anterogradely and retrogradely within axons. Focal injection of EVs containing α-synuclein into the striatum of wild-type mice results in spread of synuclein pathology to anatomically connected brain regions. Our findings suggest a scenario for late-onset PD in which lipid peroxidation promotes intracellular accumulation and then extrusion of EVs containing toxic α-synuclein species; the EVs are then internalized by adjacent neurons, so propagating the neurodegenerative process.
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