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Title: | Two different binding modes of α-synuclein to lipid vesicles depending on its aggregation state |
Authors: | Högen, Tobias Levin, Johannes Schmidt, Felix Caruana Grech Perry, Mario Vassallo, Neville Kretzschmar, Hans A. Bötzel, Kai Kamp, Frits Giese, Armin |
Keywords: | Alpha-synuclein -- Oligomerization Parkinson's disease -- Chemotherapy Parkinson's disease -- Pathogenesis Parkinson's disease -- Pathophysiology Phospholipids |
Issue Date: | 2012 |
Publisher: | Elsevier |
Citation: | Högen, T., Levin, J., Schmidt, F., Caruana, M., Vassallo, N., Kretzschmar, H.,...Giese, A. (2012). Two different binding modes of α-synuclein to lipid vesicles depending on its aggregation state. Biophysical Journal, 102(7), 1646-1655. |
Abstract: | Aggregation of α-synuclein is involved in the pathogenesis of Parkinson's disease (PD). Studies of in vitro aggregation of α-synuclein are rendered complex because of the formation of a heterogeneous population of oligomers. With the use of confocal single-molecule fluorescence techniques, we demonstrate that small aggregates (oligomers) of α-synuclein formed from unbound monomeric species in the presence of organic solvent (DMSO) and iron (Fe 3+) ions have a high affinity to bind to model membranes, regardless of the lipid-composition or membrane curvature. This binding mode contrasts with the well-established membrane binding of α-synuclein monomers, which is accompanied with α-helix formation and requires membranes with high curvature, defects in the lipid packing, and/or negatively charged lipids. Additionally, we demonstrate that membrane-bound α-synuclein monomers are protected from aggregation. Finally, we identified compounds that potently dissolved vesicle-bound α-synuclein oligomers into monomers, leaving the lipid vesicles intact. As it is commonly believed that formation of oligomers is related PD progression, such compounds may provide a promising strategy for the design of novel therapeutic drugs in Parkinson's disease. |
URI: | https://www.um.edu.mt/library/oar/handle/123456789/45983 |
Appears in Collections: | Scholarly Works - FacM&SPB |
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Two_different_binding_modes_of_α-synuclein_to_lipid_vesicles_depending_on_its_aggregation_state_2012.pdf | 1.23 MB | Adobe PDF | View/Open |
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