The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Extensive uptake of α-synuclein oligomers in astrocytes results in sustained intracellular deposits and mitochondrial damage
Abstract
The presence of Lewy bodies, mainly consisting of aggregated α-synuclein, is a pathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The α-synuclein inclusions are predominantly found in neurons, but also appear frequently in astrocytes. However, the pathological significance of α-synuclein inclusions in astrocytes and the capacity of glial cells to clear toxic α-synuclein species remain unknown. In the present study we investigated uptake, degradation and toxic effects of oligomeric α-synuclein in a co-culture system of primary neurons, astrocytes and oligodendrocytes. Alpha-synuclein oligomers were found to co-localize with the glial cells and the astrocytes were found to internalize particularly large amounts of the protein. Following ingestion, the astrocytes started to degrade the oligomers via the lysosomal pathway but, due to incomplete digestion, large intracellular deposits remained. Moreover, the astrocytes displayed mitochondrial abnormalities. Taken together, our data indicate that astrocytes play an important role in the clearance of toxic α-synuclein species from the extracellular space. However, when their degrading capacity is overburdened, α-synuclein deposits can persist and result in detrimental cellular processes.
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“The αSYN and Aβ accumulation result in severe cellular stress, indicated by lysosomal and mitochondrial deficiencies [11, 12, 23].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [23]
In the citing paper
“The concentrations were selected based on our previous studies [11, 12, 23, 28, 29].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [23]
In the citing paper
“We have previously shown that astrocytes accumulate large amounts of αSYN and Aβ aggregates, resulting in severe cellular stress [11, 12, 23, 24].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [23]
In the citing paper
“In the context of neurodegeneration, astrocytes take up aggregate-prone MAPT/tau, amyloid beta (Aβ) and SNCA (synuclein alpha), and degrade these proteins through autophagy [407–412].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [412]
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Additional file 1 of Neuronal SNCA transcription during Lewy body formation
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Self-citationDatta, I., Banerjee, R., Holla, V., Kamble, N. L., Yadav, R., & Pal, P. K. (2026) · Research Square · doi:10.21203/rs.3.rs-7255076/v1
Étude de la propagation prion-like de l'alpha-synucléine dans des réseaux de neurones reconstruits
Courte, J. (2019) · theses.fr (ABES) · doi:10.70675/95ccfbd6zedb2z4a1bz8024zb46a3ec60ebf
Study of the Neuron-Astrocyte Relationship in a Rodent Model of Tauopathy
de Gérando, A. M. (2019) · theses.fr (ABES) · doi:10.70675/04658671zaca3z4fefza24dz2f5a011bebfe
Gubinelli, F. (2019) · theses.fr (ABES) · doi:10.70675/b37261d3zcc7bz45bezb526z9e35982e09bb
Étude moléculaire de l'inflammation chronique dans la maladie de Parkinson
Compagnion, A. (2019) · theses.fr (ABES) · doi:10.70675/04ca138dz3131z4e24z884czbba2f7954a99
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Written in the Stars: Astrocyte Biology From Evolution to Disease
Falcone, C., Arckens, L., Baiula, M., Bedini, A., Bocchi, R., Broadhead, M. J., Caprini, M., Cavaliere, F., Cesca, F., Chowdhury, H. H., et al. (2026) · Acta Physiologica · doi:10.1111/apha.70289
“In addition, α-synuclein accumulation has been shown to disrupt ER–mitochondria interactions and Ca 2+ signaling, suggesting that impaired pro-teostasis and organelle crosstalk may converge to exacerbate astrocyte dysfunction [319, 320].”
Abdelaziz, A. M. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06101-6
“The cascade is initiated when pathogenic, oligomeric species of α-Syn, either released from degenerating neurons or propagating through the brain’s connectome, engage astrocytic surface receptors such as TLR2/4 or trigger intracellular oxidative stress [100].”
Abdelaziz, A. M., Fawzy, M. N., & Shokr, M. M. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06177-0
“Given that αB-crystallin is overexpressed in PD patients and animal models, it fosters the buildup of α-syn; moreover, autopsy examinations frequently reveal α-syn-positive inclusions within astrocytes, with their emergence closely mirroring the clinical advancement of PD [68].”
Influential
Metadata
- Authors
- Lindström, V., Gustafsson, G., Sanders, L. H., Howlett, E. H., Sigvardson, J., Kasrayan, A., Ingelsson, M., Bergström, J., & Erlandsson, A.
- Affiliations
- Uppsala University (SE)
- University of Pittsburgh (US)
- BioArctic Neuroscience (Sweden) (SE)
- Corresponding author
- Lindström, Veronica
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 82
- Pages
- 143-156
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W2609846517
- Cited by
- 233
- References
- 50
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 32 · 2023: 22 · 2022: 21 · 2021: 31 · 2020: 38 · 2019: 24 · 2018: 18 · 2017: 9
- FWCI
- 16.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- alpha-synuclein oligomers, astrocytes, Lewy bodies, Parkinson's disease, dementia with Lewy bodies, lysosomal degradation, mitochondrial damage, neurodegeneration
- MeSH terms
- Animals, Astrocytes, Cytoplasm, Mice, Inbred C57BL, Mitochondria, Neurons, Oligodendroglia, Parkinson Disease, Lewy Bodies, Coculture Techniques, Intracellular Space, alpha-Synuclein
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