Somatostatin binds to the human amyloid β peptide and favors the formation of distinct oligomers
- University of Toronto, Canada
- The Hospital for Sick Children, Canada
- University of Alberta, Canada
Abstract
The amyloid β peptide (Aβ) is a key player in the etiology of Alzheimer disease (AD), yet a systematic investigation of its molecular interactions has not been reported. Here we identified by quantitative mass spectrometry proteins in human brain extract that bind to oligomeric Aβ1-42 (oAβ1-42) and/or monomeric Aβ1-42 (mAβ1-42) baits. Remarkably, the cyclic neuroendocrine peptide somatostatin-14 (SST14) was observed to be the most selectively enriched oAβ1-42 binder. The binding interface comprises a central tryptophan within SST14 and the N-terminus of Aβ1-42. The presence of SST14 inhibited Aβ aggregation and masked the ability of several antibodies to detect Aβ. Notably, Aβ1-42, but not Aβ1-40, formed in the presence of SST14 oligomeric assemblies of 50 to 60 kDa that were visualized by gel electrophoresis, nanoparticle tracking analysis and electron microscopy. These findings may be relevant for Aβ-directed diagnostics and may signify a role of SST14 in the etiology of AD.
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Author details
Alejandro Ruiz-Riquelme
Gerold Schmitt-Ulms
Funding
Canadian Institutes of Health Research
- Gerold Schmitt-Ulms
Ontario Centres for Excellence
- Simon Sharpe
- Gerold Schmitt-Ulms
Alberta Innovates Bio Solutions (201600028)
- Holger Wille
- Gerold Schmitt-Ulms
Heart and Stroke Foundation of Canada (G-15-0009148)
- Simon Sharpe
Canada Foundation for Innovation
- Gerold Schmitt-Ulms
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The work was performed in strict accordance with University of Toronto animal care and biosafety recommendations. All mice were handled according to procedures approved (AUP4183.3) by the animal care committee at University Health Network overseeing work at the Krembil Discovery Centre (Toronto). The handling of samples and reagents followed biosafety procedures approved (208-S06-2) by the University of Toronto Biosafety Program.
Reviewing Editor
- Randy Schekman, Howard Hughes Medical Institute, University of California, Berkeley, United States
Publication history
- Received: November 18, 2016
- Accepted: June 14, 2017
- Accepted Manuscript published: June 26, 2017 (version 1)
- Version of Record published: July 11, 2017 (version 2)
Copyright
© 2017, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Somatostatin binds to the human amyloid β peptide and favors the formation of distinct oligomers
eLife 6:e28401.
https://doi.org/10.7554/eLife.28401
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