Extensive uptake of α-synuclein oligomers in astrocytes results in sustained intracellular deposits and mitochondrial damage.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lindström, V; Gustafsson, G; Sanders, LH; Howlett, EH; Sigvardson, J; Kasrayan, A; Ingelsson, M; Bergström, J; Erlandsson, A

Published Date

  • July 2017

Published In

Volume / Issue

  • 82 /

Start / End Page

  • 143 - 156

PubMed ID

  • 28450268

Pubmed Central ID

  • 28450268

Electronic International Standard Serial Number (EISSN)

  • 1095-9327

Digital Object Identifier (DOI)

  • 10.1016/j.mcn.2017.04.009

Language

  • eng

Conference Location

  • United States