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Optical Structural Analysis of Individual alpha-Synuclein Oligomers

Varela, JA; Rodrigues, M; De, S; Flagmeier, P; Gandhi, S; Dobson, CM; Klenerman, D; (2018) Optical Structural Analysis of Individual alpha-Synuclein Oligomers. Angewandte Chemie - International Edition , 57 (18) pp. 4886-4890. 10.1002/anie.201710779. Green open access

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Abstract

Small aggregates of misfolded proteins play a key role in neurodegenerative disorders. Such species have proved difficult to study due to the lack of suitable methods capable of resolving these heterogeneous aggregates, which are smaller than the optical diffraction limit. We demonstrate here an all‐optical fluorescence microscopy method to characterise the structure of individual protein aggregates based on the fluorescence anisotropy of dyes such as thioflavin‐T, and show that this technology is capable of studying oligomers in human biofluids such as cerebrospinal fluid. We first investigated in vitro the structural changes in individual oligomers formed during the aggregation of recombinant α‐synuclein. By studying the diffraction‐limited aggregates we directly evaluated their structural conversion and correlated this with the potential of aggregates to disrupt lipid bilayers. We finally characterised the structural features of aggregates present in cerebrospinal fluid of Parkinson's disease patients and age‐matched healthy controls.

Type: Article
Title: Optical Structural Analysis of Individual alpha-Synuclein Oligomers
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/anie.201710779
Publisher version: https://doi.org/10.1002/anie.201710779
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Physical Sciences, Chemistry, Multidisciplinary, Chemistry, amyloid fibrils, fluorescence anisotropy, neurodegeneration, Parkinson's disease, protein aggregation, THIOFLAVIN-T, AMYLOID FIBRILS, HUMAN-DISEASE, FLUORESCENCE, AGGREGATION, MECHANISM, BINDING, SURFACE
UCL classification: UCL > Provost and Vice Provost Offices
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: http://discovery.ucl.ac.uk/id/eprint/10052777
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