Glial cell death induced by overexpression of α‐synuclein
Abstract
alpha-Synuclein is present in intracellular protein aggregates that are hallmarks of common neurodegenerative disorders including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. alpha-Synuclein is localized in neurons and presynaptic terminals. Under pathological conditions, however, it is also found in glia. The role of alpha-synuclein in glial cells and its relevance to the molecular pathology of neurodegenerative diseases is presently unclear. To investigate the consequence of alpha-synuclein overexpression in glia, we transfected U373 astrocytoma cells with vectors encoding wild-type human alpha-synuclein or C-terminally truncated synuclein fused to red fluorescent protein. alpha-synuclein immunocytochemistry of transfected astroglial cells revealed diffuse cytoplasmic labeling associated with discrete inclusions both within cell bodies and processes. Susceptibility to oxidative stress was increased in astroglial cells overexpressing alpha-synuclein, particularly in the presence of cytoplasmic inclusions. Furthermore, overexpression of alpha-synuclein induced apoptotic death of astroglial cells as shown by TUNEL staining. Our in vitro model is the first to replicate salient features of the glial pathology associated with alpha-synucleinopathies. It provides a simple testbed to further explore the cascade of events that leads to apoptotic glial cell death in some of these disorders; it may also be useful to assess the effects of therapeutic interventions including antioxidative and antiapoptotic strategies.
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Gliosis in PD is atypical: astrogliosis is largely absent while microglia is highly activated.
“Gliosis in the PD is an atypical activation where astrogliosis is largely absent while the microglia is highly activated by the disease.”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Stefanova et al., 2001
Low astroglial response in PD may be caused by degeneration due to increased α-syn in astrocytes.
“The low astroglial response may be caused by degeneration due to an increase of α-syn in the astrocyte (Stefanova et al., 2001; Orr et al., 2002; Sofroniew and Vinters, 2010).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Stefanova et al., 2001
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- Authors
- Stefanova, N., Klimaschewski, L., Poewe, W., Wenning, G. K., & Reindl, M.
- Affiliations
- Universität Innsbruck (AT)
- Corresponding author
- Reindl, Markus
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2001-08-28
- Volume
- 65
- Issue
- 5
- Pages
- 432-438
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2033402586
- Cited by
- 93
- References
- 28
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 7 · 2015: 6 · 2014: 1 · 2013: 2 · 2012: 3
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- alpha-synuclein, glial cell death, astrocytes, apoptosis, oxidative stress, synucleinopathies, protein aggregation, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, neurodegeneration
- MeSH terms
- Red Fluorescent Protein, Astrocytes, Humans, Immunohistochemistry, Indicators and Reagents, L-Lactate Dehydrogenase, Luminescent Proteins, Nerve Degeneration, Nerve Tissue Proteins, Peptide Fragments, Recombinant Fusion Proteins, Transfection, Tumor Cells, Cultured, Apoptosis, Protein Structure, Tertiary, Oxidative Stress, Neurodegenerative Diseases, Cell Size, Green Fluorescent Proteins, Synucleins, alpha-Synuclein
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