Whiten, DR;
Zuo, Y;
Calo, L;
Choi, M-L;
De, S;
Flagmeier, P;
Wirthensohn, DC;
... Horrocks, MH; + view all
(2018)
Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells.
ChemBioChem
, 19
(19)
pp. 2033-2038.
10.1002/cbic.201800209.
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Abstract
The aberrant misfolding and subsequent conversion of monomeric protein into amyloid aggregates characterises many neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. These aggregates are highly heterogeneous in structure, generally of low abundance and typically smaller than the diffraction limit of light (≈250 nm). To overcome the challenges these characteristics pose to the study of endogenous aggregates formed in cells, we have developed a method to characterise them at the nanometre scale without the need for a conjugated fluorophore. Using a combination of DNA PAINT and an amyloid‐specific aptamer, we demonstrate that this technique is able to detect and super‐resolve a range of aggregated species, including those formed by α‐synuclein and amyloid‐β. Additionally, this method enables endogenous protein aggregates within cells to be characterised. We found that neuronal cells derived from patients with Parkinson's disease contain a larger number of protein aggregates than those from healthy controls.
| Type: | Article |
|---|---|
| Title: | Nanoscopic Characterisation of Individual Endogenous Protein Aggregates in Human Neuronal Cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/cbic.201800209 |
| Publisher version: | https://doi.org/10.1002/cbic.201800209 |
| Language: | English |
| Additional information: | © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | amyloid formation, aptamers, DNA PAINT, induced pluripotent stem cells, neurodegenerative disorders, alpha-synuclein |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10056034 |
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