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Is Cell Death Primary or Secondary in the Pathophysiology of Idiopathic Parkinson’s Disease?
Open AccessArticle

Toxic Oligomeric Alpha-Synuclein Variants Present in Human Parkinson’s Disease Brains Are Differentially Generated in Mammalian Cell Models

1
Chemical Engineering, Arizona State University, Tempe, AZ 85287-6106, USA
2
Division of Neurology, Barrow Neurological Institute, Phoenix, AZ 85013, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Stephan N. Witt
Biomolecules 2015, 5(3), 1634-1651; https://doi.org/10.3390/biom5031634
Received: 15 January 2015 / Revised: 17 June 2015 / Accepted: 26 June 2015 / Published: 22 July 2015
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. View Full-Text
Keywords: Parkinson’s disease; α-synuclein; aggregation; scFv antibody; neuroblastoma cells (SH-SY5Y) Parkinson’s disease; α-synuclein; aggregation; scFv antibody; neuroblastoma cells (SH-SY5Y)
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MDPI and ACS Style

Xin, W.; Emadi, S.; Williams, S.; Liu, Q.; Schulz, P.; He, P.; Alam, N.B.; Wu, J.; Sierks, M.R. Toxic Oligomeric Alpha-Synuclein Variants Present in Human Parkinson’s Disease Brains Are Differentially Generated in Mammalian Cell Models. Biomolecules 2015, 5, 1634-1651.

AMA Style

Xin W, Emadi S, Williams S, Liu Q, Schulz P, He P, Alam NB, Wu J, Sierks MR. Toxic Oligomeric Alpha-Synuclein Variants Present in Human Parkinson’s Disease Brains Are Differentially Generated in Mammalian Cell Models. Biomolecules. 2015; 5(3):1634-1651.

Chicago/Turabian Style

Xin, Wei; Emadi, Sharareh; Williams, Stephanie; Liu, Qiang; Schulz, Philip; He, Ping; Alam, Now B.; Wu, Jie; Sierks, Michael R. 2015. "Toxic Oligomeric Alpha-Synuclein Variants Present in Human Parkinson’s Disease Brains Are Differentially Generated in Mammalian Cell Models" Biomolecules 5, no. 3: 1634-1651.

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