Unveiling Amyloid-β1–42 Interaction with Zinc in Water and Mixed Hexafluoroisopropanol Solution in Alzheimer’s Disease

Unveiling Amyloid-β1–42 Interaction with Zinc in Water and Mixed Hexafluoroisopropanol... Alzheimer’s disease (AD) is a neurodegenerative disorder caused by overproduction and accumulation of amyloid beta-peptide (Aβ). The hallmarks associated with this AD are the presence of Aβ plaques between the nerve cell in the brain which leading to synaptic loss in memory. The amyloid plaques contain of transition metals like zinc, copper and iron. In a healthy brain, the metal ions are present in balance concentration. High concentrations of Zn are normally released during neurotransmission process. The release of Zn might cause the aggregation of Aβ leading to AD. Amyloid-β1–42 is the main type of Aβ in amyloid plaque. There still have limited explanation on how Aβ1–42 interaction with Zn metal, as well as the effect of Zn metal on the Aβ structure in different solvents in atomic detail. Therefore, we investigated the structural changes of Aβ1–42 in water (Aβ-H2O) and the mixed hexafluoroisopropanol (HFIP) with water (Aβ-HFIP/H2O). The mixed solvent consisted of hexafluoroisopropanol (HFIP) and water was used with the ratio of HFIP:H2O (80:20). The effect of zinc ion was also examined for the interaction of Aβ peptide with zinc in water (Aβ-Zn-H2O) and mixed solvent (Aβ-Zn-HFIP/H2O) using all atom level molecular dynamics (MD) calculations for 1 μs. We found that Aβ-Zn-HFIP/H2O contained more α-helix compared to Aβ-HFIP/H2O while Aβ-H2O and Aβ-Zn-H2O produced well-dissolved structure and they contained more β-sheets. β-turns are possible to bind with the receptor proteins and may induce the aggregation process in AD. Thus, Aβ-H2O and Aβ-Zn-H2O have higher possibility leading to AD compared to Aβ-Zn-HFIP/H2O and Aβ-HFIP/H2O models. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Peptide Research and Therapeutics Springer Journals

Unveiling Amyloid-β1–42 Interaction with Zinc in Water and Mixed Hexafluoroisopropanol Solution in Alzheimer’s Disease

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Publisher
Springer Netherlands
Copyright
Copyright © 2017 by Springer Science+Business Media New York
Subject
Life Sciences; Biochemistry, general; Animal Anatomy / Morphology / Histology; Polymer Sciences; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Molecular Medicine
ISSN
1573-3149
eISSN
1573-3904
D.O.I.
10.1007/s10989-016-9570-4
Publisher site
See Article on Publisher Site

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder caused by overproduction and accumulation of amyloid beta-peptide (Aβ). The hallmarks associated with this AD are the presence of Aβ plaques between the nerve cell in the brain which leading to synaptic loss in memory. The amyloid plaques contain of transition metals like zinc, copper and iron. In a healthy brain, the metal ions are present in balance concentration. High concentrations of Zn are normally released during neurotransmission process. The release of Zn might cause the aggregation of Aβ leading to AD. Amyloid-β1–42 is the main type of Aβ in amyloid plaque. There still have limited explanation on how Aβ1–42 interaction with Zn metal, as well as the effect of Zn metal on the Aβ structure in different solvents in atomic detail. Therefore, we investigated the structural changes of Aβ1–42 in water (Aβ-H2O) and the mixed hexafluoroisopropanol (HFIP) with water (Aβ-HFIP/H2O). The mixed solvent consisted of hexafluoroisopropanol (HFIP) and water was used with the ratio of HFIP:H2O (80:20). The effect of zinc ion was also examined for the interaction of Aβ peptide with zinc in water (Aβ-Zn-H2O) and mixed solvent (Aβ-Zn-HFIP/H2O) using all atom level molecular dynamics (MD) calculations for 1 μs. We found that Aβ-Zn-HFIP/H2O contained more α-helix compared to Aβ-HFIP/H2O while Aβ-H2O and Aβ-Zn-H2O produced well-dissolved structure and they contained more β-sheets. β-turns are possible to bind with the receptor proteins and may induce the aggregation process in AD. Thus, Aβ-H2O and Aβ-Zn-H2O have higher possibility leading to AD compared to Aβ-Zn-HFIP/H2O and Aβ-HFIP/H2O models.

Journal

International Journal of Peptide Research and TherapeuticsSpringer Journals

Published: Feb 2, 2017

References

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