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A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu(2+)-Mediated Aβ Aggregation
Copper (Cu) has been implicated in the progression of Alzheimer’s disease (AD), and aggregation of Cu and amyloid β peptide (Aβ) are considered key pathological features of AD. Metal chelators are considered to be potential therapeutic agents for AD because of their capacity to reduce metal ion-indu...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269028/ https://www.ncbi.nlm.nih.gov/pubmed/34202166 http://dx.doi.org/10.3390/ijms22136842 |
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author | Zhang, Xiaoyu Zhang, Xiancheng Zhong, Manli Zhao, Pu Guo, Chuang Li, You Xu, He Wang, Tao Gao, Huiling |
author_facet | Zhang, Xiaoyu Zhang, Xiancheng Zhong, Manli Zhao, Pu Guo, Chuang Li, You Xu, He Wang, Tao Gao, Huiling |
author_sort | Zhang, Xiaoyu |
collection | PubMed |
description | Copper (Cu) has been implicated in the progression of Alzheimer’s disease (AD), and aggregation of Cu and amyloid β peptide (Aβ) are considered key pathological features of AD. Metal chelators are considered to be potential therapeutic agents for AD because of their capacity to reduce metal ion-induced Aβ aggregation through the regulation of metal ion distribution. Here, we used phage display technology to screen, synthesize, and evaluate a novel Cu(II)-binding peptide that specifically blocked Cu-triggered Aβ aggregation. The Cu(II)-binding peptide (S-A-Q-I-A-P-H, PCu) identified from the phage display heptapeptide library was used to explore the mechanism of PCu inhibition of Cu(2+)-mediated Aβ aggregation and Aβ production. In vitro experiments revealed that PCu directly inhibited Cu(2+)-mediated Aβ aggregation and regulated copper levels to reduce biological toxicity. Furthermore, PCu reduced the production of Aβ by inhibiting Cu(2+)-induced BACE1 expression and improving Cu(II)-mediated cell oxidative damage. Cell culture experiments further demonstrated that PCu had relatively low toxicity. This Cu(II)-binding peptide that we have identified using phage display technology provides a potential therapeutic approach to prevent or treat AD. |
format | Online Article Text |
id | pubmed-8269028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82690282021-07-10 A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu(2+)-Mediated Aβ Aggregation Zhang, Xiaoyu Zhang, Xiancheng Zhong, Manli Zhao, Pu Guo, Chuang Li, You Xu, He Wang, Tao Gao, Huiling Int J Mol Sci Article Copper (Cu) has been implicated in the progression of Alzheimer’s disease (AD), and aggregation of Cu and amyloid β peptide (Aβ) are considered key pathological features of AD. Metal chelators are considered to be potential therapeutic agents for AD because of their capacity to reduce metal ion-induced Aβ aggregation through the regulation of metal ion distribution. Here, we used phage display technology to screen, synthesize, and evaluate a novel Cu(II)-binding peptide that specifically blocked Cu-triggered Aβ aggregation. The Cu(II)-binding peptide (S-A-Q-I-A-P-H, PCu) identified from the phage display heptapeptide library was used to explore the mechanism of PCu inhibition of Cu(2+)-mediated Aβ aggregation and Aβ production. In vitro experiments revealed that PCu directly inhibited Cu(2+)-mediated Aβ aggregation and regulated copper levels to reduce biological toxicity. Furthermore, PCu reduced the production of Aβ by inhibiting Cu(2+)-induced BACE1 expression and improving Cu(II)-mediated cell oxidative damage. Cell culture experiments further demonstrated that PCu had relatively low toxicity. This Cu(II)-binding peptide that we have identified using phage display technology provides a potential therapeutic approach to prevent or treat AD. MDPI 2021-06-25 /pmc/articles/PMC8269028/ /pubmed/34202166 http://dx.doi.org/10.3390/ijms22136842 Text en © 2021 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 | Article Zhang, Xiaoyu Zhang, Xiancheng Zhong, Manli Zhao, Pu Guo, Chuang Li, You Xu, He Wang, Tao Gao, Huiling A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu(2+)-Mediated Aβ Aggregation |
title | A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu(2+)-Mediated Aβ Aggregation |
title_full | A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu(2+)-Mediated Aβ Aggregation |
title_fullStr | A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu(2+)-Mediated Aβ Aggregation |
title_full_unstemmed | A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu(2+)-Mediated Aβ Aggregation |
title_short | A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu(2+)-Mediated Aβ Aggregation |
title_sort | novel cu(ii)-binding peptide identified by phage display inhibits cu(2+)-mediated aβ aggregation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269028/ https://www.ncbi.nlm.nih.gov/pubmed/34202166 http://dx.doi.org/10.3390/ijms22136842 |
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