Molecular rotors detect the formation and conversion of α-synuclein oligomers
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Supplementary information
Author(s)
Allerton, Siân C
Kuimova, Marina
Aprile, Francesco
Type
Journal Article
Abstract
α-Synuclein is an intrinsically disordered protein that forms amyloids in Parkinson’s disease. Currently, detection methods predominantly report on the formation of mature amyloids but are weakly sensitive to the early stage, toxic oligomers. Molecular rotors are fluorophores that sense changes in the viscosity of their local environment. Here, we monitor α-synuclein oligomer formation using the fluorescence lifetime of molecular rotors. We detect oligomer formation and conversion into amyloids for wild-type and two α-synuclein variants, the pathological mutant A30P and ΔP1 α-synuclein, which lacks a master regulator region of aggregation (residues 36–42). We report that A30P α-synuclein shows a rate of oligomer formation similar to that of wild-type α-synuclein, whereas ΔP1 α-synuclein shows delayed oligomer formation. Additionally, both variants demonstrate a slower conversion of oligomers into amyloids. Our method provides a quantitative approach to unveiling the complex mechanism of α-synuclein aggregation, which is key to understanding the pathology of Parkinson’s disease.
Date Issued
2025-02-19
Date Acceptance
2025-01-16
Citation
ACS Applied Materials and Interfaces, 2025, 17 (7), pp.10499-10508
ISSN
1944-8244
Publisher
American Chemical Society
Start Page
10499
End Page
10508
Journal / Book Title
ACS Applied Materials and Interfaces
Volume
17
Issue
7
Copyright Statement
© 2025 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 .
License URL
Sponsor
Medical Research Council (MRC)
Alzheimer's Research UK (ARUK)
Medical Research Council (MRC)
Identifier
10.1021/acsami.4c21710
Grant Number
MR/S033947/1
ARUK-PG2019B-020
MR/Y003616/1
Subjects
03 Chemical Sciences
09 Engineering
Nanoscience & Nanotechnology
Publication Status
Published
Date Publish Online
2025-02-05