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Extensive uptake of α-synuclein oligomers in astrocytes results in sustained intracellular deposits and mitochondrial damage.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. (Molecular geriatrics)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. (Molecular Geriatrics)
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2017 (English)In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 82, 143-156 p., S1044-7431(16)30184-1Article in journal (Refereed) Published
Abstract [en]

The presence of Lewy bodies, mainly consisting of aggregated α-synuclein, is a pathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The α-synuclein inclusions are predominantly found in neurons, but also appear frequently in astrocytes. However, the pathological significance of α-synuclein inclusions in astrocytes and the capacity of glial cells to clear toxic α-synuclein species remain unknown. In the present study we investigated uptake, degradation and toxic effects of oligomeric α-synuclein in a co-culture system of primary neurons, astrocytes and oligodendrocytes. Alpha-synuclein oligomers were found to co-localize with the glial cells and the astrocytes were found to internalize particularly large amounts of the protein. Following ingestion, the astrocytes started to degrade the oligomers via the lysosomal pathway but, due to incomplete digestion, large intracellular deposits remained. Moreover, the astrocytes displayed mitochondrial abnormalities. Taken together, our data indicate that astrocytes play an important role in the clearance of toxic α-synuclein species from the extracellular space. However, when their degrading capacity is overburdened, α-synuclein deposits can persist and result in detrimental cellular processes.

Place, publisher, year, edition, pages
2017. Vol. 82, 143-156 p., S1044-7431(16)30184-1
Keyword [en]
Astrocytes, Glia, Mitochondria, Oligodendrocytes, Parkinson's disease, α-Synuclein oligomers
National Category
Other Medical Sciences
Research subject
Medical Science; Biology with specialization in Molecular Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-326114DOI: 10.1016/j.mcn.2017.04.009PubMedID: 28450268OAI: oai:DiVA.org:uu-326114DiVA: diva2:1118809
Available from: 2017-07-02 Created: 2017-07-02 Last updated: 2017-07-05
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