A long‐lived Aβ oligomer resistant to fibrillization
Abstract
Abstract The hydrophobic Aβ peptide is highly aggregation prone; it first forms soluble oligomers, which then convert into the amyloid fibrils found in the cerebral plaques of Alzheimer's disease. It is generally understood that as the peptide concentration of Aβ increases, the fibrillization process is accelerated, but we examine the limits on this phenomenon. We found that once a threshold concentration of Aβ is exceeded, a stable oligomer is formed at the expense of fibril formation. The suppression of fibril formation was observed by amyloid‐binding dye Thioflavin T and solution nuclear magnetic resonance (NMR). Small‐angle X‐ray scattering, size exclusion chromatography, and analytical ultracentrifugation demonstrated that Aβ peptides form a range of compact species, with a dimer being an early highly populated oligomer. Solution NMR allowed us to define the secondary structure of this Aβ dimer, which shows interlocking contacts between C‐terminal peptide strands. Thus, we present a novel Aβ oligomer that resists conversion to fibrils and remains stable for more than one year.
- Authors:
-
[1]
- Department of Pharmaceutical Chemistry University of California San Francisco California
- Institute for Neurodegenerative Diseases and Department of Neurology Weill Institute for Neurosciences, University of California San Francisco California, Department of Biochemistry and Biophysics University of California San Francisco California
- Institute for Neurodegenerative Diseases and Department of Neurology Weill Institute for Neurosciences, University of California San Francisco California
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1416592
- Grant/Contract Number:
- DE‐AC02‐76SF00515
- Resource Type:
- Publisher's Accepted Manuscript
- Journal Name:
- Biopolymers
- Additional Journal Information:
- Journal Name: Biopolymers Journal Volume: 109 Journal Issue: 8; Journal ID: ISSN 0006-3525
- Publisher:
- Wiley Blackwell (John Wiley & Sons)
- Country of Publication:
- United States
- Language:
- English
Citation Formats
Nick, Mimi, Wu, Yibing, Schmidt, Nathan W., Prusiner, Stanley B., Stöhr, Jan, and DeGrado, William F. A long‐lived Aβ oligomer resistant to fibrillization. United States: N. p., 2018.
Web. doi:10.1002/bip.23096.
Nick, Mimi, Wu, Yibing, Schmidt, Nathan W., Prusiner, Stanley B., Stöhr, Jan, & DeGrado, William F. A long‐lived Aβ oligomer resistant to fibrillization. United States. https://doi.org/10.1002/bip.23096
Nick, Mimi, Wu, Yibing, Schmidt, Nathan W., Prusiner, Stanley B., Stöhr, Jan, and DeGrado, William F. Wed .
"A long‐lived Aβ oligomer resistant to fibrillization". United States. https://doi.org/10.1002/bip.23096.
@article{osti_1416592,
title = {A long‐lived Aβ oligomer resistant to fibrillization},
author = {Nick, Mimi and Wu, Yibing and Schmidt, Nathan W. and Prusiner, Stanley B. and Stöhr, Jan and DeGrado, William F.},
abstractNote = {Abstract The hydrophobic Aβ peptide is highly aggregation prone; it first forms soluble oligomers, which then convert into the amyloid fibrils found in the cerebral plaques of Alzheimer's disease. It is generally understood that as the peptide concentration of Aβ increases, the fibrillization process is accelerated, but we examine the limits on this phenomenon. We found that once a threshold concentration of Aβ is exceeded, a stable oligomer is formed at the expense of fibril formation. The suppression of fibril formation was observed by amyloid‐binding dye Thioflavin T and solution nuclear magnetic resonance (NMR). Small‐angle X‐ray scattering, size exclusion chromatography, and analytical ultracentrifugation demonstrated that Aβ peptides form a range of compact species, with a dimer being an early highly populated oligomer. Solution NMR allowed us to define the secondary structure of this Aβ dimer, which shows interlocking contacts between C‐terminal peptide strands. Thus, we present a novel Aβ oligomer that resists conversion to fibrils and remains stable for more than one year.},
doi = {10.1002/bip.23096},
journal = {Biopolymers},
number = 8,
volume = 109,
place = {United States},
year = {Wed Jan 10 00:00:00 EST 2018},
month = {Wed Jan 10 00:00:00 EST 2018}
}
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