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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...

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Autores principales: Soudy, Rania, Kimura, Ryoichi, Patel, Aarti, Fu, Wen, Kaur, Kamaljit, Westaway, David, Yang, Jing, Jhamandas, Jack
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
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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.
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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
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