title: Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation.
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.
authors: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors: Céline
authors: C
authors: Galvagnion
authors: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors: Alexander K
authors: AK
authors: Buell
authors: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors: Georg
authors: G
authors: Meisl
authors: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors: Thomas C T
authors: TC
authors: Michaels
authors: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors: Michele
authors: M
authors: Vendruscolo
authors: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors: Tuomas P J
authors: TP
authors: Knowles
authors: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors: Christopher M
authors: CM
authors: Dobson
mesh_terms: D000682:Amyloid / Q000737:chemistry; D005454:Fluorescence Polarization; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D010300:Parkinson Disease; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D000682:Amyloid; D008051:Lipid Bilayers; D008563:Membrane Lipids; D051844:alpha-Synuclein
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