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Issue 13, 2019
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Label-free detection of early oligomerization of α-synuclein and its mutants A30P/E46K through solid-state nanopores

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Abstract

A30P and E46K are two mutants of α-synuclein (α-Syn) associated with familial early-onset Parkinson's disease (PD), and amyloid fibrils of α-Syn are the hallmarks of this disease. Detecting the heterogeneous system in the oligomerization stage of α-Syn is crucial for understanding the fibril formation and in vivo toxicity of α-Syn oligomers. Over the last two decades, solid-state nanopore technology has been developed into a reliable and versatile method in single-molecule studies. In this work, we study the time-dependent kinetics of early oligomerization of wild-type α-Syn, A30P, and E46K mutants through silicon nitride solid-state nanopores. By testing A30P, E46K, and wild-type α-Syn samples with different incubation times—from 3 to 15 days—we identify three typical types of oligomers formed in the oligomerization stage and confirm that A30P and E46K mutants aggregate faster than wild-type α-Syn. The results imply that the distinct aggregation pathways and kinetics featured by wild-type α-Syn and mutations may account for their distinct cytotoxicity and pathology in PD-related studies.

Graphical abstract: Label-free detection of early oligomerization of α-synuclein and its mutants A30P/E46K through solid-state nanopores

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Supplementary files

Article information


Submitted
02 Jan 2019
Accepted
05 Mar 2019
First published
06 Mar 2019

Nanoscale, 2019,11, 6480-6488
Article type
Paper

Label-free detection of early oligomerization of α-synuclein and its mutants A30P/E46K through solid-state nanopores

X. Li, X. Tong, W. Lu, D. Yu, J. Diao and Q. Zhao, Nanoscale, 2019, 11, 6480
DOI: 10.1039/C9NR00023B

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