6533b824fe1ef96bd12800c0
RESEARCH PRODUCT
Cholesterol facilitates interactions between α‐synuclein oligomers and charge‐neutral membranes
Andreas Van MaarschalkerweerdValeria VetriBente Vestergaardsubject
AmyloidParkinson's diseaseFluorescent DyeBiophysicsPlasma protein bindingBiochemistryOligomerProtein Structure SecondaryMultiphoton microscopyMembrane phase separationCell membranechemistry.chemical_compoundGeneticStructural Biology2-NaphthylamineLaurdan fluorescenceGeneticsFluorescence microscopemedicineMolecular BiologyFluorescent DyesLaurateα-SynucleinMembranesChemistryMedicine (all)2-NaphthylamineCell MembraneMembraneCell BiologySettore FIS/07 - Fisica Applicata(Beni Culturali Ambientali Biol.e Medicin)CholesterolMembranemedicine.anatomical_structureBiophysicBiochemistryStructural biologyOligomeralpha-SynucleinParkinson’s diseaseProtein MultimerizationLaurdanLauratesProtein Bindingdescription
AbstractOligomeric species formed during α-synuclein fibrillation are suggested to be membrane-disrupting agents, and have been associated with cytotoxicity in Parkinson’s disease. The majority of studies, however, have revealed that the effect of α-synuclein oligomers is only noticeable on systems composed of anionic lipids, while the more physiologically relevant zwitterionic lipids remain intact. We present experimental evidence for significant morphological changes in zwitterionic membranes containing cholesterol, induced by α-synuclein oligomers. Depending on the lipid composition, model membranes are either unperturbed, disrupt, or undergo dramatic morphological changes and segregate into structurally different components, which we visualize by 2-photon fluorescence microscopy and generalized polarization analysis using the fluorescent probe Laurdan. Our results highlight the crucial role of cholesterol for mediating interactions between physiologically relevant membranes and α-synuclein.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-08-20 | FEBS Letters |