The investigation of copper-ion coordination to amyloid-beta and potential chelation materials for the treatment of Alzheimer’s disease
- Published
- Accepted
- Subject Areas
- Bioengineering, Bioinformatics, Biophysics, Computational Biology, Neuroscience
- Keywords
- Alzheimers, Biophysics, Chelation, Metals, AmyloidBeta, silicene, mos2, boron nitride
- Copyright
- © 2019 Pavuluru et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2019. The investigation of copper-ion coordination to amyloid-beta and potential chelation materials for the treatment of Alzheimer’s disease. PeerJ Preprints 7:e27942v2 https://doi.org/10.7287/peerj.preprints.27942v2
Abstract
Alzheimer's disease is a neurodegenerative disorder that results in the death of neurons and impaired cognitive function. One of the pathological hallmarks of Alzheimer's is the formation of senile plaques which originate from the aggregation of the Amyloid-beta protein. Recent research has found a correlation between the overabundance of copper-ions in the brain and this problem. They have hypothesized that chelation therapy may be an effective tool to solve it. In this study, we conducted Density Functional Theory calculations to investigate the interaction of the copper-ion to the truncated Amyloid-beta protein, as well as the adsorption of the copper-ion by potential chelation materials. Binding energy and charge transfer calculations were evaluated for copper's interaction with potential chelators: monolayer boron nitride, monolayer molybdenum disulfide, and monolayer silicene. Silicene produced the highest binding energies to copper, and the evidence of charge transfer between copper and the monolayer proves that there is a strong ionic bond present. Although our three monolayers did not directly present chelation potential, the absolute differences between the binding energies of the silicene binding sites and the Amyloid-beta binding sites were minimal proving that further research in silicene chelators may be useful for therapy in Alzheimer's disease.
Author Comment
The first thing that has changed about this preprint is some of the language regarding the chelation-agents. The language has been toned down to say, for example, "may be" instead of "will be". Another thing that has changed is the clarity of the methods section. This version clearly specifies that the truncated A-Beta protein was used. The final thing that has changed was the emphasis on the chelation agents. Rather than focusing on the metal-ABeta interaction, this new version puts more focus on the novel chelation agents.
Supplemental Information
Amyloid-Beta Low pH and High pH metal interactions
The etotal represents the total energy of the complex