The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells
Open accessAbstract
Post-mortem analyses of brains from patients with Parkinson disease who received fetal mesencephalic transplants show that α-synuclein-containing (α-syn-containing) Lewy bodies gradually appear in grafted neurons. Here, we explored whether intercellular transfer of α-syn from host to graft, followed by seeding of α-syn aggregation in recipient neurons, can contribute to this phenomenon. We assessed α-syn cell-to-cell transfer using microscopy, flow cytometry, and high-content screening in several coculture model systems. Coculturing cells engineered to express either GFP- or DsRed-tagged α-syn resulted in a gradual increase in double-labeled cells. Importantly, α-syn-GFP derived from 1 neuroblastoma cell line localized to red fluorescent aggregates in other cells expressing DsRed-α-syn, suggesting a seeding effect of transmitted α-syn. Extracellular α-syn was taken up by cells through endocytosis and interacted with intracellular α-syn. Next, following intracortical injection of recombinant α-syn in rats, we found neuronal uptake was attenuated by coinjection of an endocytosis inhibitor. Finally, we demonstrated in vivo transfer of α-syn between host cells and grafted dopaminergic neurons in mice overexpressing human α-syn. In summary, intercellularly transferred α-syn interacts with cytoplasmic α-syn and can propagate α-syn pathology. These results suggest that α-syn propagation is a key element in the progression of Parkinson disease pathology.
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“Particularly, the oligomeric α-Syn species appear to be prone to uptake and spread from cell-to-cell in a prion-like manner, leading to the templated misfolding of the native forms of α-Syn and formation of α-Syn aggregates throughout the brain, which are the defining pathological features of Parkinson’s disease (PD) and dementia with Lewy body (DLB) [12–19].”
From LRP1 is a neuronal receptor for α-synuclein uptake and spread (2022) · cites this paper as [18]
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“In cell culture, however, the prion-like propagation of α-synuclein lesions has been demonstrated80, 81”
From Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders (2011) · cites this paper as [81]
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Metadata
- Authors
- Hansen, C., Angot, E., Bergström, A.-L., Steiner, J. A., Pieri, L., Paul, G., Outeiro, T. F., Melki, R., Kallunki, P., Fog, K., Li, J.-Y., & Brundin, P.
- Affiliations
- Lund University (SE)
- Lundbeck (Denmark) (DK)
- Laboratoire d'Enzymologie et Biochimie Structurales (FR)
- University of Lisbon (PT)
- Corresponding author
- Brundin, Patrik
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2011-02-01
- Volume
- 121
- Issue
- 2
- Pages
- 715-725
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3026723
- OpenAlex
- W2046885195
- Cited by
- 842
- References
- 42
- Citations by year
- 2026: 13 · 2025: 26 · 2024: 25 · 2023: 31 · 2022: 43 · 2021: 69 · 2020: 70 · 2019: 59 · 2018: 51 · 2017: 72 · 2016: 68 · 2015: 68 · 2014: 64 · 2013: 77 · 2012: 64
- FWCI
- 50.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- Agence Nationale de la Recherche
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Stiftelsen Lars Hiertas Minne
- Centre National de la Recherche Scientifique
- Parkinsonfonden
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- alpha-synuclein, Parkinson's disease, Lewy bodies, intercellular transfer, endocytosis, neuroblastoma cells, intracortical injection
- MeSH terms
- Animals, Brain, Cells, Cultured, Dopamine, Humans, Neurons, Parkinson Disease, Recombinant Fusion Proteins, Lewy Bodies, Culture Media, Conditioned, Cell Transplantation, Coculture Techniques, Mice, Rats, alpha-Synuclein, HEK293 Cells
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