Journal Article PUBDB-2015-00709

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Protein/Lipid Coaggregates are Formed During $\alpha$-Synuclein-Induced Disruption of Lipid Bilayers

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2014
American Chemical Soc. Columbus, Ohio

Biomacromolecules 15(10), 3643 - 3654 () [10.1021/bm500937p]
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Abstract: Amyloid formation is associated with neurodegenerative diseases such as Parkinson’s disease (PD). Significant α-synuclein (αSN) 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 αSN is associated with dehydration of anionic lipid membranes and stimulation of protein secondary structure. As a result of membrane fragmentation, soluble αSN:-lipid coaggregates are formed, hence, suggesting a novel molecular mechanism behind PD amyloid cytotoxicity.

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Note: (c) American Chemical Society. Post referee full text in progress.

Contributing Institute(s):
  1. EMBL-User (EMBL-User)
  2. EMBL (EMBL)
Research Program(s):
  1. DORIS Beamline D1.2 (POF2-54G13) (POF2-54G13)
  2. PETRA Beamline P12 (POF2-54G14) (POF2-54G14)
  3. 6G3 - PETRA III (POF3-622) (POF3-622)
Experiment(s):
  1. DORIS Beamline D1.2 (DORIS III)
  2. PETRA Beamline P12 (PETRA III)

Appears in the scientific report 2014
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Medline ; BIOSIS Previews ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
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 Record created 2015-01-16, last modified 2025-07-30


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