Cargando…
Molecular Mechanism of Cyanidin-3-O-Glucoside Disassembling Aβ Fibril In Silico
The deposition of β-amyloid (Aβ) in the brain leads to neurotoxic effects and subsequent Alzheimer’s disease (AD). While AD is becoming more and more prevalent in modern society, therapeutic efforts targeting Aβ could be a promising solution. Currently, two natural products are reported to disintegr...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9824066/ https://www.ncbi.nlm.nih.gov/pubmed/36615767 http://dx.doi.org/10.3390/nu15010109 |
_version_ | 1784866317502775296 |
---|---|
author | Gao, Jihui Fu, Jiahui Gao, Xiaoyu Yang, Dong |
author_facet | Gao, Jihui Fu, Jiahui Gao, Xiaoyu Yang, Dong |
author_sort | Gao, Jihui |
collection | PubMed |
description | The deposition of β-amyloid (Aβ) in the brain leads to neurotoxic effects and subsequent Alzheimer’s disease (AD). While AD is becoming more and more prevalent in modern society, therapeutic efforts targeting Aβ could be a promising solution. Currently, two natural products are reported to disintegrate preformed Aβ fibril in vitro. Meanwhile, the chemical driving force behind this phenomenon remains unknown. Taking cyanidin-3-O-glucoside (Cy-3G) as an example, here we studied its interaction with different Aβ polymorphs in silico. Negative charges on different Aβ polymorphs draw the interaction with the flavylium cation on Cy-3G. Our results show that Aβ in a single peptide form in solution exposed more hydrophobic solvent accessible surface area than its fibril structure (per protomer), and Cy-3G interacts more intensively with the single peptide form than fibril as indicated by more hydrogen bonding formed and more amino acid residues involved in their hydrophobic interactions. Thus, the single Aβ peptide aggregation into fibril and fibril dissociation into single peptide equilibrium could be disturbed by the preferential binding of Cy-3G to the monomeric Aβ peptide, which leads to the disassembly of the pathogenic Aβ fibril. This study offers a novel perspective of Cy-3G alleviated AD syndrome beyond its dogmatic antioxidant activity. |
format | Online Article Text |
id | pubmed-9824066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98240662023-01-08 Molecular Mechanism of Cyanidin-3-O-Glucoside Disassembling Aβ Fibril In Silico Gao, Jihui Fu, Jiahui Gao, Xiaoyu Yang, Dong Nutrients Communication The deposition of β-amyloid (Aβ) in the brain leads to neurotoxic effects and subsequent Alzheimer’s disease (AD). While AD is becoming more and more prevalent in modern society, therapeutic efforts targeting Aβ could be a promising solution. Currently, two natural products are reported to disintegrate preformed Aβ fibril in vitro. Meanwhile, the chemical driving force behind this phenomenon remains unknown. Taking cyanidin-3-O-glucoside (Cy-3G) as an example, here we studied its interaction with different Aβ polymorphs in silico. Negative charges on different Aβ polymorphs draw the interaction with the flavylium cation on Cy-3G. Our results show that Aβ in a single peptide form in solution exposed more hydrophobic solvent accessible surface area than its fibril structure (per protomer), and Cy-3G interacts more intensively with the single peptide form than fibril as indicated by more hydrogen bonding formed and more amino acid residues involved in their hydrophobic interactions. Thus, the single Aβ peptide aggregation into fibril and fibril dissociation into single peptide equilibrium could be disturbed by the preferential binding of Cy-3G to the monomeric Aβ peptide, which leads to the disassembly of the pathogenic Aβ fibril. This study offers a novel perspective of Cy-3G alleviated AD syndrome beyond its dogmatic antioxidant activity. MDPI 2022-12-26 /pmc/articles/PMC9824066/ /pubmed/36615767 http://dx.doi.org/10.3390/nu15010109 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Gao, Jihui Fu, Jiahui Gao, Xiaoyu Yang, Dong Molecular Mechanism of Cyanidin-3-O-Glucoside Disassembling Aβ Fibril In Silico |
title | Molecular Mechanism of Cyanidin-3-O-Glucoside Disassembling Aβ Fibril In Silico |
title_full | Molecular Mechanism of Cyanidin-3-O-Glucoside Disassembling Aβ Fibril In Silico |
title_fullStr | Molecular Mechanism of Cyanidin-3-O-Glucoside Disassembling Aβ Fibril In Silico |
title_full_unstemmed | Molecular Mechanism of Cyanidin-3-O-Glucoside Disassembling Aβ Fibril In Silico |
title_short | Molecular Mechanism of Cyanidin-3-O-Glucoside Disassembling Aβ Fibril In Silico |
title_sort | molecular mechanism of cyanidin-3-o-glucoside disassembling aβ fibril in silico |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9824066/ https://www.ncbi.nlm.nih.gov/pubmed/36615767 http://dx.doi.org/10.3390/nu15010109 |
work_keys_str_mv | AT gaojihui molecularmechanismofcyanidin3oglucosidedisassemblingabfibrilinsilico AT fujiahui molecularmechanismofcyanidin3oglucosidedisassemblingabfibrilinsilico AT gaoxiaoyu molecularmechanismofcyanidin3oglucosidedisassemblingabfibrilinsilico AT yangdong molecularmechanismofcyanidin3oglucosidedisassemblingabfibrilinsilico |