A peptide binding to the β-site of APP improves spatial memory and attenuates Aβ burden in Alzheimer's disease transgenic mice.
Amyloid precursor protein cleaving enzyme 1 (BACE1), an aspartyl protease, initiates processing of the amyloid precursor protein (APP) into β-amyloid (Aβ); the peptide likely contributes to development of Alzheimer's disease (AD). BACE1 is an attractive therapeutic target for AD treatment, but...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3486805?pdf=render |
| _version_ | 1819209177230213120 |
|---|---|
| author | Shi-gao Yang Shao-wei Wang Min Zhao Ran Zhang Wei-wei Zhou Ya-nan Li Ya-jing Su He Zhang Xiao-lin Yu Rui-tian Liu |
| author_facet | Shi-gao Yang Shao-wei Wang Min Zhao Ran Zhang Wei-wei Zhou Ya-nan Li Ya-jing Su He Zhang Xiao-lin Yu Rui-tian Liu |
| author_sort | Shi-gao Yang |
| collection | DOAJ |
| description | Amyloid precursor protein cleaving enzyme 1 (BACE1), an aspartyl protease, initiates processing of the amyloid precursor protein (APP) into β-amyloid (Aβ); the peptide likely contributes to development of Alzheimer's disease (AD). BACE1 is an attractive therapeutic target for AD treatment, but it exhibits other physiological activities and has many other substrates besides APP. Thus, inhibition of BACE1 function may cause adverse side effects. Here, we present a peptide, S1, isolated from a peptide library that selectively inhibits BACE1 hydrolytic activity by binding to the β-proteolytic site on APP and Aβ N-terminal. The S1 peptide significantly reduced Aβ levels in vitro and in vivo and inhibited Aβ cytotoxicity in SH-SY5Y cells. When applied to APPswe/PS1dE9 double transgenic mice by intracerebroventricular injection, S1 significantly improved the spatial memory as determined by the Morris Water Maze, and also attenuated their Aβ burden. These results indicate that the dual-functional peptide S1 may have therapeutic potential for AD by both reducing Aβ generation and inhibiting Aβ cytotoxicity. |
| first_indexed | 2024-12-23T05:51:08Z |
| format | Article |
| id | doaj.art-58a0526d4f8244bbad4355bb720da5f0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T05:51:08Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-58a0526d4f8244bbad4355bb720da5f02022-12-21T17:57:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4854010.1371/journal.pone.0048540A peptide binding to the β-site of APP improves spatial memory and attenuates Aβ burden in Alzheimer's disease transgenic mice.Shi-gao YangShao-wei WangMin ZhaoRan ZhangWei-wei ZhouYa-nan LiYa-jing SuHe ZhangXiao-lin YuRui-tian LiuAmyloid precursor protein cleaving enzyme 1 (BACE1), an aspartyl protease, initiates processing of the amyloid precursor protein (APP) into β-amyloid (Aβ); the peptide likely contributes to development of Alzheimer's disease (AD). BACE1 is an attractive therapeutic target for AD treatment, but it exhibits other physiological activities and has many other substrates besides APP. Thus, inhibition of BACE1 function may cause adverse side effects. Here, we present a peptide, S1, isolated from a peptide library that selectively inhibits BACE1 hydrolytic activity by binding to the β-proteolytic site on APP and Aβ N-terminal. The S1 peptide significantly reduced Aβ levels in vitro and in vivo and inhibited Aβ cytotoxicity in SH-SY5Y cells. When applied to APPswe/PS1dE9 double transgenic mice by intracerebroventricular injection, S1 significantly improved the spatial memory as determined by the Morris Water Maze, and also attenuated their Aβ burden. These results indicate that the dual-functional peptide S1 may have therapeutic potential for AD by both reducing Aβ generation and inhibiting Aβ cytotoxicity.http://europepmc.org/articles/PMC3486805?pdf=render |
| spellingShingle | Shi-gao Yang Shao-wei Wang Min Zhao Ran Zhang Wei-wei Zhou Ya-nan Li Ya-jing Su He Zhang Xiao-lin Yu Rui-tian Liu A peptide binding to the β-site of APP improves spatial memory and attenuates Aβ burden in Alzheimer's disease transgenic mice. PLoS ONE |
| title | A peptide binding to the β-site of APP improves spatial memory and attenuates Aβ burden in Alzheimer's disease transgenic mice. |
| title_full | A peptide binding to the β-site of APP improves spatial memory and attenuates Aβ burden in Alzheimer's disease transgenic mice. |
| title_fullStr | A peptide binding to the β-site of APP improves spatial memory and attenuates Aβ burden in Alzheimer's disease transgenic mice. |
| title_full_unstemmed | A peptide binding to the β-site of APP improves spatial memory and attenuates Aβ burden in Alzheimer's disease transgenic mice. |
| title_short | A peptide binding to the β-site of APP improves spatial memory and attenuates Aβ burden in Alzheimer's disease transgenic mice. |
| title_sort | peptide binding to the β site of app improves spatial memory and attenuates aβ burden in alzheimer s disease transgenic mice |
| url | http://europepmc.org/articles/PMC3486805?pdf=render |
| work_keys_str_mv | AT shigaoyang apeptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT shaoweiwang apeptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT minzhao apeptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT ranzhang apeptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT weiweizhou apeptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT yananli apeptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT yajingsu apeptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT hezhang apeptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT xiaolinyu apeptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT ruitianliu apeptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT shigaoyang peptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT shaoweiwang peptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT minzhao peptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT ranzhang peptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT weiweizhou peptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT yananli peptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT yajingsu peptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT hezhang peptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT xiaolinyu peptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice AT ruitianliu peptidebindingtothebsiteofappimprovesspatialmemoryandattenuatesabburdeninalzheimersdiseasetransgenicmice |