1. Observation of an α-synuclein liquid droplet state and its maturation into Lewy body-like assemblies
- Author
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Christopher M. Dobson, Samuel T. Dada, Maarten C. Hardenberg, Elizabeth A Robinson, Monika Fuxreiter, Sam Casford, Gabriele S. Kaminski Schierle, Clemens F Kaminksi, Tessa Sinnige, Michele Vendruscolo, Ellen A. A. Nollen, Chetan Poudel, Vendruscolo, Michele [0000-0002-3616-1610], Apollo - University of Cambridge Repository, and Molecular Neuroscience and Ageing Research (MOLAR)
- Subjects
0301 basic medicine ,Parkinson's disease ,Arrested maturation ,Amyloid ,Synaptic vesicle ,Animals, Genetically Modified ,03 medical and health sciences ,0302 clinical medicine ,α-synuclein ,liquid‒liquid phase separation ,mental disorders ,Genetics ,medicine ,Animals ,Humans ,Maturation process ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Molecular Biology ,Medicine(all) ,biology ,Lewy body ,Chemistry ,Parkinson Disease ,Cell Biology ,General Medicine ,Articles ,biology.organism_classification ,medicine.disease ,Amyloid fibril ,In vitro ,nervous system diseases ,Disease Models, Animal ,030104 developmental biology ,030220 oncology & carcinogenesis ,Biophysics ,alpha-Synuclein ,α synuclein ,Lewy Bodies - Abstract
Misfolded α-synuclein is a major component of Lewy bodies, which are a hallmark of Parkinson’s disease. A large body of evidence shows that α-synuclein can self-assemble into amyloid fibrils, but the relationship between amyloid formation and Lewy body formation still remains unclear. Here we show, both in vitro and in a C. elegans model of Parkinson’s disease, that α-synuclein undergoes liquid-liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel. This maturation process towards the amyloid state is delayed in the presence of model synaptic vesicles in vitro. Taken together, these results suggest that the formation of Lewy bodies is linked to the arrested maturation of α-synuclein condensates in the presence of lipids and other cellular components.
- Published
- 2021
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