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Cited by 661Parkinson's Disease Mechanisms and TreatmentsAlzheimer's disease research and treatmentsLipid Membrane Structure and Behavior

Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation

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Galvagnion, Céline, Buell, Alexander K, Meisl, Georg, Michaels, Thomas C T, Vendruscolo, Michele, Knowles, Tuomas P J, Dobson, Christopher M·2015·Nature Chemical Biology
DOI 10.1038/nchembio.1750PMC PMC5019199
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Abstract

α-Synuclein (α-syn) is a 140-residue intrinsically disordered protein that is involved in neuronal and synaptic vesicle plasticity, but its aggregation to form amyloid fibrils is the hallmark of Parkinson's disease (PD). The interaction between α-syn and lipid surfaces is believed to be a key feature for mediation of its normal function, but under other circumstances it is able to modulate amyloid fibril formation. Using a combination of experimental and theoretical approaches, we identify the mechanism through which facile aggregation of α-syn is induced under conditions where it binds a lipid bilayer, and we show that the rate of primary nucleation can be enhanced by three orders of magnitude or more under such conditions. These results reveal the key role that membrane interactions can have in triggering conversion of α-syn from its soluble state to the aggregated state that is associated with neurodegeneration and to its associated disease states.

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  • Lipid vesicles accelerate the nucleation of α-synuclein aggregation by ×1000.

    “Another relevant case is the reported ×1000 acceleration of the nucleation of α-synuclein aggregation by lipid vesicles [186].”

    From Systems protobiology: origin of life in lipid catalytic networks (2018) · cites this paper as [186]

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Cited by

Sorted by citations

Authors
Galvagnion, C., Buell, A. K., Meisl, G., Michaels, T. C. T., Vendruscolo, M., Knowles, T. P. J., & Dobson, C. M.
Affiliations
University of Cambridge (GB)
Corresponding author
Dobson, Christopher M
ORCID
Venue
Nature Chemical Biology
Publisher
Springer Science and Business Media LLC
Published
2015-02-02
Volume
11
Issue
3
Pages
229-234
ISSN
  • 1552-4450 (ISSN-L)
  • 1552-4469
DOI
10.1038/nchembio.1750
PMC
PMC5019199
OpenAlex
W2072675976
Cited by
661
References
4
Citations by year
2026: 53 · 2025: 59 · 2024: 73 · 2023: 59 · 2022: 69 · 2021: 67 · 2020: 65 · 2019: 61 · 2018: 55 · 2017: 42 · 2016: 39 · 2015: 19
FWCI
36.43
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Chemical Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Apollo (University of Cambridge) (acceptedVersion)
Funders
  • Wellcome Trust (089703, 094425/Z/10/Z)
  • Biotechnology and Biological Sciences Research Council (BB/H003843/1, BB/J002119/1)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
alpha-synuclein, protein aggregation, primary nucleation, lipid vesicles, DMPS, negatively charged lipids, amyloid fibril formation, Parkinson's disease, Lewy bodies, intrinsically disordered proteins, protein-lipid interactions, membrane interactions, neurodegeneration
MeSH terms
Amyloid, Fluorescence Polarization, Kinetics, Lipid Bilayers, Membrane Lipids, Parkinson Disease, alpha-Synuclein

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