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Preparation, Purification, and Use of Fatty Acid-containing Liposomes
Published on: February 9, 2018
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Large fatty acid-derived Aβ42 oligomers form ring-like assemblies.
Wenhui Xi1, Dexter N Dean2, Kelli A Stockmal3
1Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, USA.
The Journal of Chemical Physics
|February 24, 2019
Summary
Large Fatty Acid-derived Oligomers (LFAOs) of amyloid-beta (Aβ) exhibit distinct structures and neurotoxicity. Understanding these Aβ oligomer structures offers molecular insights into Alzheimer disease (AD) pathology.
Area of Science:
- Neuroscience
- Biochemistry
- Structural Biology
Background:
- Alzheimer disease (AD) is primarily caused by toxic low molecular weight oligomers of amyloid-beta (Aβ).
- Understanding Aβ oligomer structure is crucial for elucidating AD molecular pathology.
- Previous work showed Aβ42 peptides form Large Fatty Acid-derived Oligomers (LFAOs) (12-24mers) in the presence of fatty acids.
Purpose of the Study:
- To determine the detailed structures of 12mer and 24mer LFAOs.
- To investigate the functional differences and similarities between 12mer and 24mer LFAOs.
- To correlate structural findings with observed biophysical and cellular properties.
Main Methods:
- Molecular dynamic simulations.
- Biophysical measurements.
- Structural analysis of Aβ oligomers.
Main Results:
- LFAOs predominantly exist as 12mers at low and 24mers at high concentrations.
- 12mer LFAOs are more neurotoxic and self-replicating than 24mer LFAOs.
- 12mers form double-layered hexamer rings (6x2), and 24mers form double-layered dodecamer rings (12x2).
- Aβ units adopt an S-shaped conformation within LFAOs.
- Concentration and pH-dependent reorganization underlies LFAO assembly and properties.
Conclusions:
- The study elucidates the distinct structures of 12mer and 24mer LFAOs.
- Structural differences explain the varying neurotoxicity and propagation mechanisms of LFAOs.
- Findings provide molecular insights into Aβ oligomer formation and its role in Alzheimer disease pathogenesis.
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