Cargando…
Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model
Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662706/ https://www.ncbi.nlm.nih.gov/pubmed/31358858 http://dx.doi.org/10.1038/s41598-019-47255-9 |
_version_ | 1783439695196192768 |
---|---|
author | Soudy, Rania Kimura, Ryoichi Patel, Aarti Fu, Wen Kaur, Kamaljit Westaway, David Yang, Jing Jhamandas, Jack |
author_facet | Soudy, Rania Kimura, Ryoichi Patel, Aarti Fu, Wen Kaur, Kamaljit Westaway, David Yang, Jing Jhamandas, Jack |
author_sort | Soudy, Rania |
collection | PubMed |
description | Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY within the peptides is an essential sequence for preservation of the beneficial effects of the fragments that we report here and constitutes a new pharmacological target. These findings suggest that the amylin receptor antagonism may represent a novel therapy for AD. |
format | Online Article Text |
id | pubmed-6662706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66627062019-08-02 Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model Soudy, Rania Kimura, Ryoichi Patel, Aarti Fu, Wen Kaur, Kamaljit Westaway, David Yang, Jing Jhamandas, Jack Sci Rep Article Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY within the peptides is an essential sequence for preservation of the beneficial effects of the fragments that we report here and constitutes a new pharmacological target. These findings suggest that the amylin receptor antagonism may represent a novel therapy for AD. Nature Publishing Group UK 2019-07-29 /pmc/articles/PMC6662706/ /pubmed/31358858 http://dx.doi.org/10.1038/s41598-019-47255-9 Text en © The Author(s) 2019, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Soudy, Rania Kimura, Ryoichi Patel, Aarti Fu, Wen Kaur, Kamaljit Westaway, David Yang, Jing Jhamandas, Jack Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model |
title | Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model |
title_full | Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model |
title_fullStr | Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model |
title_full_unstemmed | Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model |
title_short | Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model |
title_sort | short amylin receptor antagonist peptides improve memory deficits in alzheimer’s disease mouse model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662706/ https://www.ncbi.nlm.nih.gov/pubmed/31358858 http://dx.doi.org/10.1038/s41598-019-47255-9 |
work_keys_str_mv | AT soudyrania shortamylinreceptorantagonistpeptidesimprovememorydeficitsinalzheimersdiseasemousemodel AT kimuraryoichi shortamylinreceptorantagonistpeptidesimprovememorydeficitsinalzheimersdiseasemousemodel AT patelaarti shortamylinreceptorantagonistpeptidesimprovememorydeficitsinalzheimersdiseasemousemodel AT fuwen shortamylinreceptorantagonistpeptidesimprovememorydeficitsinalzheimersdiseasemousemodel AT kaurkamaljit shortamylinreceptorantagonistpeptidesimprovememorydeficitsinalzheimersdiseasemousemodel AT westawaydavid shortamylinreceptorantagonistpeptidesimprovememorydeficitsinalzheimersdiseasemousemodel AT yangjing shortamylinreceptorantagonistpeptidesimprovememorydeficitsinalzheimersdiseasemousemodel AT jhamandasjack shortamylinreceptorantagonistpeptidesimprovememorydeficitsinalzheimersdiseasemousemodel |