Department
neurobiology
Document Type
Article
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.
Publication Date
7-22-2015
Publication Title
Biomolecules
ISSN
2218273X
Volume
5
Issue
3
First Page
1634
Last Page
1651
Digital Object Identifier (DOI)
10.3390/biom5031634
Recommended Citation
Xin, Wei; Emadi, Sharareh; Williams, Stephanie; Liu, Qiang; Schulz, Philip; He, Ping; Alam, Now Bahar; Wu, Jie; and Sierks, Michael R., "Toxic Oligomeric Alpha-Synuclein Variants Present In Human Parkinson’S Disease Brains Are Differentially Generated In Mammalian Cell Models" (2015). Translational Neuroscience. 175.
https://scholar.barrowneuro.org/neurobiology/175