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- Title
Toxic Oligomeric Alpha-Synuclein Variants Present in Human Parkinson's Disease Brains Are Differentially Generated in Mammalian Cell Models.
- Authors
Xin, Wei; Emadi, Sharareh; Williams, Stephanie; Liu, Qiang; Schulz, Philip; He, Ping; Alam, Now Bahar; Wu, Jie; Sierks, Michael R.
- Abstract
Misfolding and aggregation of α-synuclein into toxic soluble oligomeric α-synuclein aggregates has been strongly correlated with the pathogenesis of Parkinson's disease (PD). Here, we show that two different morphologically distinct oligomeric α-synuclein aggregates are present in human post-mortem PD brain tissue and are responsible for the bulk of α-synuclein induced toxicity in brain homogenates from PD samples. Two antibody fragments that selectively bind the different oligomeric α-synuclein variants block this α-synuclein induced toxicity and are useful tools to probe how various cell models replicate the α-synuclein aggregation pattern of human PD brain. Using these reagents, we show that mammalian cell type strongly influences α-synuclein aggregation, where neuronal cells best replicate the PD brain α-synuclein aggregation profile. Overexpression of α-synuclein in the different cell lines increased protein aggregation but did not alter the morphology of the oligomeric aggregates generated. Differentiation of the neuronal cells into a cholinergic-like or dopaminergic-like phenotype increased the levels of oligomeric α-synuclein where the aggregates were localized in cell neurites and cell bodies.
- Subjects
PARKINSON'S disease; ALPHA-synuclein; MAMMALIAN cell cycle
- Publication
Biomolecules (2218-273X), 2015, Vol 5, Issue 3, p1634
- ISSN
2218-273X
- Publication type
Article
- DOI
10.3390/biom5031634