Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/45983
Title: Two different binding modes of α-synuclein to lipid vesicles depending on its aggregation state
Authors: Högen, Tobias
Levin, Johannes
Schmidt, Felix
Caruana, 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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