A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu(2+)-Mediated Aβ Aggregation.
A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu(2+)-Mediated Aβ Aggregation.
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噬菌体展示鉴定的新型 Cu(II) 结合肽抑制 Cu2 介导的 Aβ 聚集
DOI：
10.3390/ijms22136842
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发表时间：
2021-06-25
影响因子：
5.6
通讯作者：
Gao H
中科院分区：
文献类型：
--
作者：
Zhang X;Zhang X;Zhong M;Zhao P;Guo C;Li Y;Xu H;Wang T;Gao H
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 Cu2+-mediated Aβ aggregation and Aβ production. In vitro experiments revealed that PCu directly inhibited Cu2+-mediated Aβ aggregation and regulated copper levels to reduce biological toxicity. Furthermore, PCu reduced the production of Aβ by inhibiting Cu2+-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.
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DOI：
10.1073/pnas.1911153117
发表时间：
2020-05-12
影响因子：
11.1
作者：
Jia, Zhiguang;Schmit, Jeremy D.;Chen, Jianhan
通讯作者：
Chen, Jianhan
影响因子：
11.4
作者：
Cheignon C;Tomas M;Bonnefont-Rousselot D;Faller P;Hureau C;Collin F
通讯作者：
Collin F
影响因子：
5.6
作者：
Gao J;Suo C;Tseng JH;Moss MA;Terry AV Jr;Chapman J
通讯作者：
Chapman J
影响因子：
3.2
作者：
Guilloreau, Luc;Combalbert, Sarah;Faller, Peter
通讯作者：
Faller, Peter
影响因子：
2.9
作者：
Jiang, Dianlu;Men, Lijie;Zhou, Feimeng
通讯作者：
Zhou, Feimeng