Uptake and mitochondrial dysfunction of alpha-synuclein in human astrocytes, cortical neurons and fibroblasts
Open accessAbstract
The accumulation and aggregation of alpha-synuclein (α-syn) in several tissue including the brain is a major pathological hallmark in Parkinson’s disease (PD). In this study, we show that α-syn can be taken up by primary human cortical neurons, astrocytes and skin-derived fibroblasts in vitro. Our findings that brain and peripheral cells exposed to α-syn can lead to impaired mitochondrial function, leading to cellular degeneration and cell death, provides additional evidence for the involvement of mitochondrial dysfunction as a mechanism of toxicity of α-syn in human cells.
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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.
“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 [411]
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References 44 · Cited by 91
Research works printed but not linked: 1
- Guillemin G Smythe G Takikawa O Brew BJ Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes and neurons Glia 2004 49 15 23 15390107
- Authors
- Braidy, N., Gai, W.-P., Xu, Y. H., Sachdev, P., Guillemin, G. J., Jiang, X.-M., Ballard, J. W. O., Horan, M. P., Fang, Z. M., Chong, B. H., & Chan, D. Y.
- Affiliations
- Bankstown Lidcombe Hospital (AU)
- Flinders University (AU)
- UNSW Sydney (AU)
- Corresponding author
- Chan, DanielKam Yin
- ORCID
- Venue
- Translational Neurodegeneration
- Published
- 2013-10-04
- Volume
- 2
- Issue
- 1
- Pages
- 20-20
- ISSN
- 2047-9158 (ISSN-L)
- PMC
- PMC3853407
- OpenAlex
- W2149259509
- Cited by
- 91
- References
- 44
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 9 · 2023: 11 · 2022: 15 · 2021: 10 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 2 · 2013: 1
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Translational Neurodegeneration (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- Flinders Academic Commons (Flinders University) (submittedVersion)
- Flinders Academic Commons (Flinders University) (submittedVersion, cc-by)
- Funders
- Alzheimer's Association (IIRG-08-89545)
- University of New South Wales
- Medical Research Council
- National Health and Medical Research Council (IIRG-08-89545)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- alpha-synuclein, Parkinson's disease, mitochondrial dysfunction, protein uptake, astrocytes, cortical neurons, fibroblasts, cell death, neurodegeneration
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