期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 82, 期 -, 页码 143-156出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2017.04.009
关键词
alpha-Synuclein oligomers; Astrocytes; Oligodendrocytes; Parkinson's disease; Glia; Mitochondria
资金
- Swedish Research Council [2015-02671]
- Swedish Parkinson Foundation [931/16]
- Swedish Alzheimer Foundation [AF-646541]
- U4 Ageing Brain network
- Ahlen Foundation [mC27h16, mA17/h14]
- Dementia Association Foundation
- Hedlunds Foundation [M-2016-0291]
- Magn Bergwalls stiftelse [2016-01714]
- William N. & Bernice E. Bumpus Foundation Innovation Award
- Marianne and Marcus Wallenberg Foundation
- Swedish Brain Foundation
- Parkinson Research Foundation
- King Gustaf V and Queen Victoria's Foundation of Freemasons
- Uppsala Berzelii Center
- Swedish Research Council [2015-02671] Funding Source: Swedish Research Council
The presence of Lewy bodies, mainly consisting of aggregated a-synuclein, is a pathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The alpha-synuclein inclusions are predominantly found in neurons, but also appear frequently in astrocytes. However, the pathological significance of alpha-synuclein inclusions in astrocytes and the capacity of glial cells to clear toxic alpha-synuclein species remain unknown. In the present study we investigated uptake, degradation and toxic effects of oligomeric alpha-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 alpha-synuclein species from the extracellular space. However, when their degrading capacity is overburdened, alpha-synuclein deposits can persist and result in detrimental cellular processes. (C) 2017 Elsevier Inc. All rights reserved.
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