Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Xiaoyu, Zhang, Xiancheng, Zhong, Manli, Zhao, Pu, Guo, Chuang, Li, You, Xu, He, Wang, Tao, Gao, Huiling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1783720484553097216
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
work_keys_str_mv AT zhangxiaoyu anovelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT zhangxiancheng anovelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT zhongmanli anovelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT zhaopu anovelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT guochuang anovelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT liyou anovelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT xuhe anovelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT wangtao anovelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT gaohuiling anovelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT zhangxiaoyu novelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT zhangxiancheng novelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT zhongmanli novelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT zhaopu novelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT guochuang novelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT liyou novelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT xuhe novelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT wangtao novelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation
AT gaohuiling novelcuiibindingpeptideidentifiedbyphagedisplayinhibitscu2mediatedabaggregation