Intracellular alpha-synuclein affects early maturation of primary oligodendrocyte progenitor cells
Open accessAbstract
Myelin loss is a widespread neuropathological hallmark of the atypical parkinsonian disorder multiple system atrophy (MSA). On a cellular level, MSA is characterized by alpha-synuclein (aSyn)-positive glial cytoplasmic inclusions (GCIs) within mature oligodendrocytes leading to demyelination as well as axonal and neuronal loss. Oligodendrocyte progenitor cells (OPCs) represent a proliferative cell population distributed throughout the adult mammalian central nervous system. During remyelination, OPCs are recruited to sites of demyelination, differentiate, and finally replace dysfunctional mature oligodendrocytes. However, comprehensive studies investigating OPCs and remyelination processes in MSA are lacking. In the present study, we therefore investigate the effect of human aSyn (h-aSyn) on early primary rat OPC maturation. Upon lentiviral transduction, h-aSyn expressing OPCs exhibit fewer and shorter primary processes at the initiation of differentiation. Until day 4 of a 6day differentiation paradigm, h-aSyn expressing OPCs further show a severely delayed maturation evidenced by reduced myelin gene expression and increased levels of the progenitor marker platelet derived growth factor receptor-alpha (PDGFRα). Matching these results, OPCs that take up extracellular recombinant h-aSyn exhibit a similar delayed differentiation. In both experimental setups however, myelin gene expression is restored at day 6 of differentiation paralleled by decreased intracellular h-aSyn levels indicating a reverse correlation of h-aSyn and the differentiation potential of OPCs. Taken together, these findings suggest a tight link between the intracellular level of h-aSyn and maturation capacity of primary OPCs.
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Overexpression of α-syn in cell culture models dramatically impaired the maturation of 2 separate oligodendrocyte precursor cell lines, shown by significant reductions of MBP during maturation.
“In support of this, overexpression of α-syn in cell culture models dramatically impaired the maturation of 2 separate oligodendrocyte precursor cell lines, shown by significant reductions of MBP during maturation [13].”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [13]
The Results (‘Interference of h-aSyn with primary OPC maturation’; page unavailable) report significantly reduced MBP during early differentiation after h-aSyn expression, with levels restored by day 6. But this study used primary rat OPC cultures, not two separate OPC cell lines; the Discussion identifies the CG4 cell-line finding as an earlier study. (LLM, conf=0.90)
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- Authors
- Ettle, B., Reiprich, S., Deusser, J., Schlachetzki, J. C. M., Xiang, W., Prots, I., Masliah, E., Winner, B., Wegner, M., & Winkler, J.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University of California San Diego (US)
- Corresponding author
- Winkler, Jürgen
- ORCID
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 62
- Pages
- 68-78
- ISSN
- 1044-7431 (ISSN-L)
- PMC
- PMC4170075
- OpenAlex
- W2057720588
- Cited by
- 57
- References
- 52
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 12 · 2019: 2 · 2018: 5 · 2017: 7 · 2016: 7 · 2015: 5
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Interdisciplinary Center of Clinical Research
- IZKF (TP E18:, N3)
- Bavarian State Ministry of Education and Culture, Science and Arts
- Bavarian Research Network Induced Pluripotent Stem Cells (ForIPS)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- alpha-synuclein, oligodendrocyte precursor cells, oligodendrocyte differentiation, remyelination, multiple system atrophy, myelin gene expression, PDGFRA, demyelination, lentiviral transduction, glial cytoplasmic inclusions
- MeSH terms
- Animals, Axons, Cell Differentiation, Cells, Cultured, Demyelinating Diseases, Myelin Basic Protein, Myelin Sheath, Oligodendroglia, Rats, Wistar, Intracellular Space, alpha-Synuclein, Neural Stem Cells
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