Protein/Lipid Coaggregates are Formed During 伪-Synuclein-Induced Disruption of Lipid Bilayers
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- 作者：Andreas van Maarschalkerweerd ; Valeria Vetri ; Annette Eva Langkilde ; Vito Foder脿 ; Bente Vestergaard
- 刊名：Biomacromolecules
- 出版年：2014
- 出版时间：October 13, 2014
- 年：2014
- 卷：15
- 期：10
- 页码：3643-3654
- 全文大小：598K
- ISSN：1526-4602
文摘
Amyloid formation is associated with neurodegenerative diseases such as Parkinson鈥檚 disease (PD). Significant 伪-synuclein (伪SN) deposition in lipid-rich Lewy bodies is a hallmark of PD. Nonetheless, an unraveling of the connection between neurodegeneration and amyloid fibrils, including the molecular mechanisms behind potential amyloid-mediated toxic effects, is still missing. Interaction between amyloid aggregates and the lipid cell membrane is expected to play a key role in the disease progress. Here, we present experimental data based on hybrid analysis of two-photon-microscopy, solution small-angle X-ray scattering and circular dichroism data. Data show in real time changes in liposome morphology and stability upon protein addition and reveal that membrane disruption mediated by amyloidogenic 伪SN is associated with dehydration of anionic lipid membranes and stimulation of protein secondary structure. As a result of membrane fragmentation, soluble 伪SN:-lipid coaggregates are formed, hence, suggesting a novel molecular mechanism behind PD amyloid cytotoxicity.