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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In the citing paper
“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]
Citations
Cites
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In vivo demonstration that α-synuclein oligomers are toxic
Winner, B., Jappelli, R., Maji, S. K., Desplats, P. A., Boyer, L., Aigner, S., Hetzer, C., Loher, T., Vilar, M., Campioni, S., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100976108 · Cited by 1,463
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The lysosome: from waste bag to potential therapeutic target
Appelqvist, H., Wäster, P., Kågedal, K., & Öllinger, K. (2013) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjt022 · Cited by 772
Different Species of α-Synuclein Oligomers Induce Calcium Influx and Seeding
Danzer, K. M., Haasen, D., Karow, A. R., Moussaud, S., Habeck, M., Giese, A., Kretzschmar, H., Hengerer, B., & Kostka, M. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2617-07.2007 · Cited by 765
Toll‐like receptor 4 is required for α‐synuclein dependent activation of microglia and astroglia
Fellner, L., Irschick, R., Schanda, K., Reindl, M., Klimaschewski, L., Poewe, W., Wenning, G. K., & Stefanova, N. (2013) · Glia · doi:10.1002/glia.22437 · Cited by 697
Research works printed but not linked: 1
- Lööv, 2012, Engulfing astrocytes protect neurons from contact-induced apoptosis following injury, PLoS One, 7, 10.1371/journal.pone.0033090 · DOI
Cited by
Sorted by citations
Neuroinflammation in the central nervous system: Symphony of glial cells
Yang, Q., & Zhou, J. (2018) · Glia · doi:10.1002/glia.23571 · Cited by 539
“The aggregated proteins in glial cells cause detrimental cellular processes, such as mitochondrial abnormalities, and disrupt basic intracellular protein degradation systems (Fellner, Jellinger, Wenning, & Stefanova, 2011; Lindstrom et al., 2017).”
BackgroundNew insights into the complex role of mitochondria in Parkinson’s disease
Grünewald, A., Kumar, K. R., & Sue, C. M. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.09.003 · Cited by 375
“In a recent series of publications by the Erlandsson lab, uptake, degradation and toxicity of oligomeric alpha-synuclein were tested in a co-culture system of mouse primary neurons, astrocytes and oligodendrocytes (Lindstrom et al., 2017).”
BackgroundAlpha-synuclein oligomers: a new hope
Bengoa‐Vergniory, N., Roberts, R. F., Wade‐Martins, R., & Alegre‐Abarrategui, J. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1755-1 · Cited by 349
Human Astrocytes Transfer Aggregated Alpha-Synuclein via Tunneling Nanotubes
Rostami, J., Holmqvist, S., Lindström, V., Sigvardson, J., Westermark, G. T., Ingelsson, M., Bergström, J., Roybon, L., & Erlandsson, A. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.0983-17.2017 · Cited by 339
“This concentration was chosen based on our previous investigations of neuronal– glial cocultures, demonstrating that astrocytes rapidly internalized particularly large amounts of -SYN oligomers (Lindström et al., 2017).”
MethodSelf-citationSengupta, U., & Kayed, R. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102270 · Cited by 318
“PSP, PD, DLB and ALS, where microglia and astrocytes play important roles in neuroinflammation (Alster et al., 2020; Amin et al., 2020; Bachiller et al., 2018; GuzmanMartinez et al., 2019; Lindstrom et al., 2017).”
Background
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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