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Human Astrocytes Transfer Aggregated Alpha-Synuclein via Tunneling Nanotubes
Open accessAbstract
Many lines of evidence suggest that the Parkinson's disease (PD)-related protein α-synuclein (α-SYN) can propagate from cell to cell in a prion-like manner. However, the cellular mechanisms behind the spreading remain elusive. Here, we show that human astrocytes derived from embryonic stem cells actively transfer aggregated α-SYN to nearby astrocytes via direct contact and tunneling nanotubes (TNTs). Failure in the astrocytes' lysosomal digestion of excess α-SYN oligomers results in α-SYN deposits in the trans-Golgi network followed by endoplasmic reticulum swelling and mitochondrial disturbances. The stressed astrocytes respond by conspicuously sending out TNTs, enabling intercellular transfer of α-SYN to healthy astrocytes, which in return deliver mitochondria, indicating a TNT-mediated rescue mechanism. Using a pharmacological approach to inhibit TNT formation, we abolished the transfer of both α-SYN and mitochondria. Together, our results highlight the role of astrocytes in α-SYN cell-to-cell transfer, identifying possible pathophysiological events in the PD brain that could be of therapeutic relevance. SIGNIFICANCE STATEMENT Astrocytes are the major cell type in the brain, yet their role in Parkinson's disease progression remains elusive. Here, we show that human astrocytes actively transfer aggregated α-synuclein (α-SYN) to healthy astrocytes via direct contact and tunneling nanotubes (TNTs), rather than degrade it. The astrocytes engulf large amounts of oligomeric α-SYN that are subsequently stored in the trans-Golgi network region. The accumulation of α-SYN in the astrocytes affects their lysosomal machinery and induces mitochondrial damage. The stressed astrocytes respond by sending out TNTs, enabling intercellular transfer of α-SYN to healthy astrocytes. Our findings highlight an unexpected role of astrocytes in the propagation of α-SYN pathology via TNTs, revealing astrocytes as a potential target for therapeutic intervention.
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“In the AD and PD brain, both astrocytes and microglia acquire reactive, inflammatory phenotypes and can effectively phagocytose aggregated proteins and cell debris, as well as secrete various cytokines and inflammatory mediators [8–13].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [11]
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“Subsequently, stressed astrocytes respond by sending out tunneling nanotubes (TNTs), enabling intercellular transfer of pathogenic protein aggregates, as well as MHCII complexes to nearby cells [11, 24].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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 [11]
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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 [11]
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“These observations are in line with our previous discoveries that astrocytes easily degrade αSYN and Aβ monomers, while they accumulate larger oligomers and fibrils [11, 12].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [11]
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“Our previous results indicate that astrocytes are capable of transferring αSYN as well as MHCII to other astrocytes via direct membrane contact and through TNTs, implicating astrocytes as one of the important players in propagation of αSYN pathology [11, 24].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Microglia and astrocytes are known to be responsible for many inflammatory processes in affected brains, including phagocytosis of αSYN and Aβ aggregates, secretion of inflammatory mediators, and stimulation of the innate immune system [8–12].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [11]
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“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 [11]
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“We have previously reported that cultured astrocytes accumulate αSYN and Aβ aggregates but not the monomeric form of the proteins [11, 12].”
From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [11]
In the citing paper
“iii) αSyn has the ability to spread to adjacent cells via secretion in exosomes [209], uptake via endocytosis [210] and cell-surface receptors like HSPGs, or even direct neuron-to-neuron [211, 212] or astrocyte-to-neuron [213] transfer via tunneling nanotubes (Fig. 2).”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [213]
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Cites
Spillantini, M. G., Schmidt, M. L., Lee, V. M.-Y., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997) · Nature · doi:10.1038/42166 · Cited by 8,382
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
Astrocytes: Biology and pathology
Sofroniew, M. V., & Vinters, H. V. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0619-8 · Cited by 5,196
Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., & Goedert, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6469 · Cited by 2,868
Nanotubular Highways for Intercellular Organelle Transport
Rustom, A., Saffrich, R., Markovic, I., Walther, P., & Gerdes, H.-H. (2004) · Science · doi:10.1126/science.1093133 · Cited by 2,038
Li, J.-Y., Englund, E., Holton, J. L., Soulet, D., Hagell, P., Lees, A. J., Lashley, T., Quinn, N. P., Rehncrona, S., Björklund, A., et al. (2008) · Nature Medicine · doi:10.1038/nm1746 · Cited by 1,845
Lewy body–like pathology in long-term embryonic nigral transplants in Parkinson's disease
Kordower, J. H., Chu, Y., Hauser, R. A., Freeman, T. B., & Olanow, C. W. (2008) · Nature Medicine · doi:10.1038/nm1747 · Cited by 1,722
Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein
Desplats, P., Lee, H.-J., Bae, E.-J., Patrick, C., Rockenstein, E., Crews, L., Spencer, B., Masliah, E., & Lee, S.-J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903691106 · Cited by 1,485
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
α-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson's Models
Cooper, A. A., Gitler, A. D., Cashikar, A. G., Haynes, C. M., Hill, K. J., Bhullar, B., Liu, K., Xu, K., Strathearn, K. E., Liu, F., et al. (2006) · Science · doi:10.1126/science.1129462 · Cited by 1,411
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Items 301–341 of 341
Eltom, K., Mothes, T., Libard, S., Ingelsson, M., & Erlandsson, A. (2024) · Figshare · doi:10.6084/m9.figshare.26685720
Self-citationMothes, T., Portal, B., Konstantinidis, E., Eltom, K., Libard, S., Streubel-Gallasch, L., Ingelsson, M., Rostami, J., Lindskog, M., & Erlandsson, A. (2024) · Figshare · doi:10.6084/m9.figshare.26598038
Self-citationAltay, M. F., Liu, A. K. L., Holton, J. L., Parkkinen, L., & Lashuel, H. A. (2022) · Figshare · doi:10.6084/m9.figshare.21547375
Eltom, K., Mothes, T., Libard, S., Ingelsson, M., & Erlandsson, A. (2024) · Figshare · doi:10.6084/m9.figshare.26685738
Self-citationEltom, K., Mothes, T., Libard, S., Ingelsson, M., & Erlandsson, A. (2024) · Figshare · doi:10.6084/m9.figshare.26685729
Self-citationMothes, T., Portal, B., Konstantinidis, E., Eltom, K., Libard, S., Streubel-Gallasch, L., Ingelsson, M., Rostami, J., Lindskog, M., & Erlandsson, A. (2024) · Figshare · doi:10.6084/m9.figshare.26598029
Self-citationZyśk, M., Beretta, C., Naia, L., Dakhel, A., Påvénius, L., Brismar, H., Lindskog, M., Ankarcrona, M., & Erlandsson, A. (2023) · Figshare · doi:10.6084/m9.figshare.22610225
Self-citationMothes, T., Portal, B., Konstantinidis, E., Eltom, K., Libard, S., Streubel-Gallasch, L., Ingelsson, M., Rostami, J., Lindskog, M., & Erlandsson, A. (2024) · Figshare · doi:10.6084/m9.figshare.26598041
Self-citationEltom, K., Mothes, T., Libard, S., Ingelsson, M., & Erlandsson, A. (2024) · Figshare · doi:10.6084/m9.figshare.26685747
Self-citationIntercellular Transfer of PTBP1 Drives Human Neural Stem Cell FatePreprint
Capobianco, D. L., Palma, F. D., Filomena, E., Lasconi, C., Pousis, C., Simeone, L., Proto, F., Profico, D. C., Gelati, M., Picardi, E., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.19.706765
Datta, I., Banerjee, R., Holla, V., Kamble, N. L., Yadav, R., & Pal, P. K. (2026) · Research Square · doi:10.21203/rs.3.rs-7255076/v1
Li, D., Liu, X., Zhang, L., Gong, Q., Huang, W., & Xu, Y. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-07868-x
Development of Inhibitors of Amyloid Fibril Propagation
Bendifallah, M. (2019) · theses.fr (ABES) · doi:10.70675/a872e5bdzc153z41f4z9472z725fd78aab48
Study of the role of Rab proteins and their effectors on Tunneling nanotubes
Bhat, S. (2019) · theses.fr (ABES) · doi:10.70675/7fee92a1zc615z4de9z87cdz4ac590863df0
Study of the Neuron-Astrocyte Relationship in a Rodent Model of Tauopathy
de Gérando, A. M. (2019) · theses.fr (ABES) · doi:10.70675/04658671zaca3z4fefza24dz2f5a011bebfe
Architecture of Tunneling Nanotubes : a Structural Approach
Cervantes, D. C. (2019) · theses.fr (ABES) · doi:10.70675/7134eee8z8acdz4e45za0afz00069cdc5443
Bouvier‐Müller, A. (2020) · theses.fr (ABES) · doi:10.70675/2097d129z95aaz45f5zbf91z199fddefb42c
Étude moléculaire de l'inflammation chronique dans la maladie de Parkinson
Compagnion, A. (2019) · theses.fr (ABES) · doi:10.70675/04ca138dz3131z4e24z884czbba2f7954a99
Étude de la propagation de l'alpha-synucléine de l'hôte vers le greffon dans la maladie de Parkinson
Patrigeon, M. (2022) · theses.fr (ABES) · doi:10.70675/8d75463az5b67z46bfz8649zc3e016dabdda
Dakhel, A., Mothes, T., Eltom, K., Michno, W., & Erlandsson, A. (2026) · iScience · doi:10.1016/j.isci.2026.115819
Self-citationExosomes in Amyloid Propagation—Roles in Neurodegeneration
Mishra, R., & Upadhyay, A. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05913-w
Mitochondria transfer in neurological disorders: the key role of neuroglia
Jiao, J., Chen, H., Verkhratsky, A., Su, Y., & Yi, C. (2026) · Molecular Neurodegeneration · doi:10.1186/s13024-026-00953-1 · Cited by 2
Characterization of a distinct form of vimentin in the neurodegenerative brain
Dakhel, A., Vestin, J., Giedraitis, V., Nyholm, D., Ingelsson, M., & Erlandsson, A. (2026) · Acta Neuropathologica Communications · doi:10.1186/s40478-026-02324-9
Self-citationN, R. K. A., Sreenivas, B. K. A., Varshith, M. R., Mundada, R. R., Padmanabhan, S., Jain, S., Kambaru, A., Dastidar, S. G., Padavattan, S., Rao, V. K., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.23.727344
Propagation of α-synuclein pathology: models, mechanisms and future goals
Zolin, A., Weber, S. A., Xie, Y. X., & Burré, J. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00038-9
Du, X., & Deng, Y. (2026) · Journal of Visualized Experiments · doi:10.3791/71670
Glial control of extracellular α-synuclein propagation in LRRK2 Parkinson’s disease
Datta, I., & Sahu, D. D. (2026) · Advances in immunology · doi:10.1016/bs.ai.2026.04.005
Nanotubular networks in the aging brain: from neuroprotection to neurodegeneration
Jategaonkar, M. S., Miller, N. H., Zur, S., Geula, C., Penzes, P., & Zaccard, C. R. (2026) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2026.1864090
Miller, W. B., Baluška, F., Slijepčević, P., & Reber, A. S. (2026) · Springer eBooks · doi:10.1007/978-3-032-23779-8_5
Kashyap, R., Sreenivas, B. K. A., Varshith, M. R., Mundada, R. R., Padmanabhan, S., Jain, S., Kambaru, A., Dastidar, S. G., Padavattan, S., Rao, V. K., et al. (2026) · Cell & Bioscience · doi:10.1186/s13578-026-01617-9
Glucosylceramides trigger the shedding of alpha-synuclein laden ectosomes
Tegeder, I. (2026) · Extracellular Vesicles and Circulating Nucleic Acids · doi:10.20517/evcna.2026.51
Nanotubes enable intercellular communication in early-branching eukaryotes
Suma, H. R., Kay, R. R., Eswarappa, S. M., & Stallforth, P. (2026) · PNAS Nexus · doi:10.1093/pnasnexus/pgag238
Astrocytes in Parkinson’s disease: Beyond support, toward therapy
Wu, S., Wang, W., Yang, L., Pan, S., Thomas, E. R., & Li, X. (2026) · Experimental Neurology · doi:10.1016/j.expneurol.2026.115964
Abdelaziz, A. M. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06101-6
Therapeutic targeting of tauopathies: From druggable biology to precision intervention
Zhang, C., Ma, J., Wu, X., Wang, X., Huang, X., Zheng, H., & Zhao, Y. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108432
Astrocytes in Neurodegeneration: Spatial States, Crosstalk, and Emerging Therapies
Steger, L., Rothhammer, V., & Zunke, F. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06142-x
LeeBae, J., Bopp, V., Goreth, A., Grozdanov, V., Engels, Z., Kühlwein, J. K., Gazzola, E., Rombach, D., Meier, L., Dimou, L., et al. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00046-9
Abdelaziz, A. M., Fawzy, M. N., & Shokr, M. M. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06177-0
Liu, Y., Halliday, G. M., & Fu, Y. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.06.757209
Tian, X., Zhang, B., Wang, Y., & Wei, J. (2026) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2026.102961
Meade, R. M. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.2017355
Metadata
- Authors
- Rostami, J., Holmqvist, S., Lindström, V., Sigvardson, J., Westermark, G. T., Ingelsson, M., Bergström, J., Roybon, L., & Erlandsson, A.
- Affiliations
- Uppsala University (SE)
- Lund University (SE)
- Corresponding author
- Erlandsson, Anna
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2017-10-31
- Volume
- 37
- Issue
- 49
- Pages
- 11835-11853
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC5719970
- OpenAlex
- W2765364382
- Cited by
- 339
- References
- 75
- Citations by year
- 2026: 45 · 2025: 30 · 2024: 64 · 2023: 47 · 2022: 34 · 2021: 38 · 2020: 26 · 2019: 31 · 2018: 24
- FWCI
- 15.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Åke Wiberg Stiftelse
- Innovationsfonden
- Vetenskapsrådet
- 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, Parkinson's disease, tunneling nanotubes, astrocytes, prion-like propagation, intercellular transfer, lysosomal degradation, trans-Golgi network, mitochondrial damage, endoplasmic reticulum stress, mitochondrial transfer
- MeSH terms
- Astrocytes, Cell Communication, Cells, Cultured, Humans, Nanotubes, alpha-Synuclein, Embryonic Stem Cells
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