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Alpha-Synuclein Cell-to-Cell Transfer and Seeding in Grafted Dopaminergic Neurons In Vivo
Open accessAbstract
Several people with Parkinson's disease have been treated with intrastriatal grafts of fetal dopaminergic neurons. Following autopsy, 10-22 years after surgery, some of the grafted neurons contained Lewy bodies similar to those observed in the host brain. Numerous studies have attempted to explain these findings in cell and animal models. In cell culture, α-synuclein has been found to transfer from one cell to another, via mechanisms that include exosomal transport and endocytosis, and in certain cases seed aggregation in the recipient cell. In animal models, transfer of α-synuclein from host brain cells to grafted neurons has been shown, but the reported frequency of the event has been relatively low and little is known about the underlying mechanisms as well as the fate of the transferred α-synuclein. We now demonstrate frequent transfer of α-synuclein from a rat brain engineered to overexpress human α-synuclein to grafted dopaminergic neurons. Further, we show that this model can be used to explore mechanisms underlying cell-to-cell transfer of α-synuclein. Thus, we present evidence both for the involvement of endocytosis in α-synuclein uptake in vivo, and for seeding of aggregation of endogenous α-synuclein in the recipient neuron by the transferred α-synuclein. Finally, we show that, at least in a subset of the studied cells, the transmitted α-synuclein is sensitive to proteinase K. Our new model system could be used to test compounds that inhibit cell-to-cell transfer of α-synuclein and therefore might retard progression of Parkinson neuropathology.
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“Others have shown in vitro and in vivo that alpha-synuclein is transmitted via endocytosis to neighboring neurons (Angot et al., 2012;Desplats et al., 2009).”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Angot et al., 2012
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Metadata
- Authors
- Angot, E., Steiner, J. A., Lema Tomé, C. M., Ekström, P., Mattsson, B., Björklund, A., & Brundin, P.
- Affiliations
- Van Andel Institute (US)
- Lund University (SE)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-06-21
- Volume
- 7
- Issue
- 6
- Pages
- e39465
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3380846
- OpenAlex
- W1973113152
- Cited by
- 270
- References
- 45
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 15 · 2021: 22 · 2020: 30 · 2019: 24 · 2018: 19 · 2017: 28 · 2016: 27 · 2015: 23 · 2014: 23 · 2013: 27 · 2012: 3
- FWCI
- 15.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- Rosenberg Foundation
- Strong
- Lunds Universitet
- Vetenskapsrådet
- 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, cell-to-cell transmission, seeding, Parkinson's disease, intrastriatal transplantation, Lewy bodies, endocytosis, exosomes, proteinase K sensitivity, alpha-synuclein overexpression, alpha-synuclein aggregation, rat model
- MeSH terms
- Animals, Brain, Cell Communication, Cell Survival, Disease Models, Animal, Dopamine, Female, Gene Expression Regulation, Humans, Parkinson Disease, Phosphorylation, Lewy Bodies, Rats, Sprague-Dawley, Endopeptidase K, Rats, alpha-Synuclein, Dopaminergic Neurons
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