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Research at St Andrews

Optical structural analysis of individual α-synuclein oligomers

Research output: Contribution to journalArticlepeer-review

Author(s)

Juan A Varela, Margarida Rodrigues, Suman De, Patrick Flagmeier, Sonia Gandhi, Christopher M Dobson, David Klenerman, Steven F Lee

School/Research organisations

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.

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Details

Original languageEnglish
Pages (from-to)4886-4890
Number of pages5
JournalAngewandte Chemie International Edition
Volume57
Issue number18
Early online date23 Mar 2018
DOIs
Publication statusPublished - 23 Apr 2018

    Research areas

  • Amyloid fibrils, Fluorescence anisotropy, Neurodegenratio, Parkinson's disease

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