Alpha-Synuclein Expression in the Oligodendrocyte Lineage: an In Vitro and In Vivo Study Using Rodent and Human Models
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In this study, we sought evidence for alpha-synuclein (ASYN) expression in oligodendrocytes, as a possible endogenous source of ASYN to explain its presence in glial inclusions found in multiple system atrophy (MSA) and Parkinson's disease (PD). We identified ASYN in oligodendrocyte lineage progenitors isolated from the rodent brain, in oligodendrocytes generated from embryonic stem cells, and in induced pluripotent stem cells produced from fibroblasts of a healthy individual and patients diagnosed with MSA or PD, in cultures in vitro. Notably, we observed a significant decrease in ΑSYN during oligodendrocyte maturation. Additionally, we show the presence of transcripts in PDGFRΑ/CD140a(+) cells and SOX10(+) oligodendrocyte lineage nuclei isolated by FACS from rodent and human healthy and diseased brains, respectively. Our work identifies ASYN in oligodendrocyte lineage cells, and it offers additional in vitro cellular models that should provide significant insights of the functional implication of ASYN during oligodendrocyte development and disease.
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Oligodendrocytes differentiated from iPSCs derived from MSA patients expressed α-syn, whereas iPSCs from PD and healthy controls do not.
“In contrast, oligodendrocytes differentiated from induced pluripotent stem cells (iPSCs) derived from MSA patients expressed α-syn, whereas iPSCs from PD and healthy controls do not [10]”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [10]
The Results section is titled “Oligodendrocytes Generated from iPSCs from a Healthy Individual and Patients with PD or MSA Also Express SNCA,” contrary to the claimed absence in PD and healthy controls. The Discussion likewise reports α-synuclein expression across diseased and healthy iPSC backgrounds, though it decreases as oligodendrocytes mature. Page numbers are not provided in our copy. (LLM, conf=0.94)
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- Authors
- Djelloul, M., Holmqvist, S., Boza-Serrano, A., Azevedo, C., Yeung, M. S., Goldwurm, S., Frisén, J., Deierborg, T., & Roybon, L.
- Affiliations
- Lund University (SE)
- Karolinska Institutet (SE)
- Istituti Clinici di Perfezionamento (IT)
- Corresponding author
- Roybon, Laurent
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 5
- Issue
- 2
- Pages
- 174-184
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC4618831
- OpenAlex
- W2119594652
- Cited by
- 138
- References
- 28
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 17 · 2023: 12 · 2022: 13 · 2021: 14 · 2020: 16 · 2019: 12 · 2018: 15 · 2017: 11 · 2016: 12 · 2015: 2
- FWCI
- 9.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- Innovationsfonden
- Strong
- Lunds Universitet
- Thorsten och Elsa Segerfalks Stiftelse
- Parkinsonfonden
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- alpha-synuclein, oligodendrocytes, multiple system atrophy, Parkinson's disease, glial inclusions, oligodendrocyte maturation, induced pluripotent stem cells, embryonic stem cells, SOX10
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Humans, Oligodendroglia, Species Specificity, Cell Lineage, Mice, alpha-Synuclein, Embryonic Stem Cells, Induced Pluripotent Stem Cells, Neural Stem Cells
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