| Autor: |
Dong C; Department of Physics, University of Alberta, Edmonton, AB, Canada.; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Hoffmann M; Department of Physics, University of Alberta, Edmonton, AB, Canada., Li X; Department of Physics, University of Alberta, Edmonton, AB, Canada.; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Wang M; Department of Physics, University of Alberta, Edmonton, AB, Canada.; National Research Council, National Institute of Nanotechnology, University of Alberta, Edmonton, AB, Canada., Garen CR; Department of Physics, University of Alberta, Edmonton, AB, Canada., Petersen NO; Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Woodside MT; Department of Physics, University of Alberta, Edmonton, AB, Canada. michael.woodside@ualberta.ca.; National Research Council, National Institute of Nanotechnology, University of Alberta, Edmonton, AB, Canada. michael.woodside@ualberta.ca. |
| Abstrakt: |
Pre-fibrillar oligomers of α-synuclein are thought to be pathogenic molecules leading to neurotoxicity associated with Parkinson's disease and other neurodegenerative disorders. However, small oligomers are difficult to isolate for study. To gain better insight into the properties of small α-synuclein oligomers, we investigated engineered oligomers of specific size (dimers, tetramers, and octamers) linked head-to-tail in tandem, comparing the behavior of the oligomers to monomeric α-synuclein. All oligomeric constructs remained largely disordered in solution, as determined from dynamic light scattering and size-exclusion chromatography. Electron microscopy revealed that each construct could aggregate to form fibrils similar to those formed by monomeric α-synuclein. The interactions with large unilamellar vesicles (LUVs) composed of negatively-charged lipids differed depending on size, with smaller oligomers forming more extensive helical structure as determined by CD spectroscopy. Monitoring the influx of a fluorescence bleaching agent into vesicles showed that larger oligomers were somewhat more effective at degrading vesicular integrity and inducing membrane permeabilization. |
