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A Novel Heptapeptide, GPPGPAG Transfers to the Brain, and Ameliorates Memory Dysfunction and Dendritic Atrophy in Alzheimer’s Disease Model Mice
We investigated the effects of a heptapeptide, GPPGPAG, on memory improvement and neuritic regeneration in Alzheimer’s disease models to evaluate its potency as a new anti-Alzheimer’s disease (AD) therapy. The anti-AD effects of GPPGPAG were evaluated in Aβ-treated cortical neurons and 5XFAD, a mous...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160438/ https://www.ncbi.nlm.nih.gov/pubmed/34054554 http://dx.doi.org/10.3389/fphar.2021.680652 |
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author | Tohda, Chihiro Kogure, Chisato Nomoto, Kaori de Toledo, Andreia Yang, Ximeng Hirano, Eiichi |
author_facet | Tohda, Chihiro Kogure, Chisato Nomoto, Kaori de Toledo, Andreia Yang, Ximeng Hirano, Eiichi |
author_sort | Tohda, Chihiro |
collection | PubMed |
description | We investigated the effects of a heptapeptide, GPPGPAG, on memory improvement and neuritic regeneration in Alzheimer’s disease models to evaluate its potency as a new anti-Alzheimer’s disease (AD) therapy. The anti-AD effects of GPPGPAG were evaluated in Aβ-treated cortical neurons and 5XFAD, a mouse model of AD. Exposure of cortical neurons to Aβ25-35 for 3 days resulted in atrophy of axons and dendrites. Treatment with GPPGPAG improved the dendritic atrophy of Aβ-treated cortical neurons, but not axonal atrophy. Postsynaptic and presynaptic densities under Aβ1-42 exposure were increased by GPPGPAG post treatment. Oral administration of GPPGPAG to 5XFAD mice for 15 days improved significantly object recognition memory and dendritic density. Direct infusion of GPPGPAG into the lateral ventricle of 5XFAD mice for 28 days improved object recognition memory. Following oral administration of GPPGPAG in mice, the undigested heptapeptide was detected in the plasma and cerebral cortex. Analysis of target protein of GPPGPAG in neurons by DARTS method identified 14-3-3ε as a bound protein. The protective effect of GPPGPAG on Aβ1-42-induced dendritic atrophy was canceled by knockdown of 14-3-3ε. Taken together, these results suggest that GPPGPAG is orally available, transfers to the brain, and ameliorates memory dysfunction in AD brain, which is possibly mediated by 14-3-3ε-related dendritic restoration. |
format | Online Article Text |
id | pubmed-8160438 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81604382021-05-29 A Novel Heptapeptide, GPPGPAG Transfers to the Brain, and Ameliorates Memory Dysfunction and Dendritic Atrophy in Alzheimer’s Disease Model Mice Tohda, Chihiro Kogure, Chisato Nomoto, Kaori de Toledo, Andreia Yang, Ximeng Hirano, Eiichi Front Pharmacol Pharmacology We investigated the effects of a heptapeptide, GPPGPAG, on memory improvement and neuritic regeneration in Alzheimer’s disease models to evaluate its potency as a new anti-Alzheimer’s disease (AD) therapy. The anti-AD effects of GPPGPAG were evaluated in Aβ-treated cortical neurons and 5XFAD, a mouse model of AD. Exposure of cortical neurons to Aβ25-35 for 3 days resulted in atrophy of axons and dendrites. Treatment with GPPGPAG improved the dendritic atrophy of Aβ-treated cortical neurons, but not axonal atrophy. Postsynaptic and presynaptic densities under Aβ1-42 exposure were increased by GPPGPAG post treatment. Oral administration of GPPGPAG to 5XFAD mice for 15 days improved significantly object recognition memory and dendritic density. Direct infusion of GPPGPAG into the lateral ventricle of 5XFAD mice for 28 days improved object recognition memory. Following oral administration of GPPGPAG in mice, the undigested heptapeptide was detected in the plasma and cerebral cortex. Analysis of target protein of GPPGPAG in neurons by DARTS method identified 14-3-3ε as a bound protein. The protective effect of GPPGPAG on Aβ1-42-induced dendritic atrophy was canceled by knockdown of 14-3-3ε. Taken together, these results suggest that GPPGPAG is orally available, transfers to the brain, and ameliorates memory dysfunction in AD brain, which is possibly mediated by 14-3-3ε-related dendritic restoration. Frontiers Media S.A. 2021-05-14 /pmc/articles/PMC8160438/ /pubmed/34054554 http://dx.doi.org/10.3389/fphar.2021.680652 Text en Copyright © 2021 Tohda, Kogure, Nomoto, Toledo, Yang and Hirano. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Tohda, Chihiro Kogure, Chisato Nomoto, Kaori de Toledo, Andreia Yang, Ximeng Hirano, Eiichi A Novel Heptapeptide, GPPGPAG Transfers to the Brain, and Ameliorates Memory Dysfunction and Dendritic Atrophy in Alzheimer’s Disease Model Mice |
title | A Novel Heptapeptide, GPPGPAG Transfers to the Brain, and Ameliorates Memory Dysfunction and Dendritic Atrophy in Alzheimer’s Disease Model Mice |
title_full | A Novel Heptapeptide, GPPGPAG Transfers to the Brain, and Ameliorates Memory Dysfunction and Dendritic Atrophy in Alzheimer’s Disease Model Mice |
title_fullStr | A Novel Heptapeptide, GPPGPAG Transfers to the Brain, and Ameliorates Memory Dysfunction and Dendritic Atrophy in Alzheimer’s Disease Model Mice |
title_full_unstemmed | A Novel Heptapeptide, GPPGPAG Transfers to the Brain, and Ameliorates Memory Dysfunction and Dendritic Atrophy in Alzheimer’s Disease Model Mice |
title_short | A Novel Heptapeptide, GPPGPAG Transfers to the Brain, and Ameliorates Memory Dysfunction and Dendritic Atrophy in Alzheimer’s Disease Model Mice |
title_sort | novel heptapeptide, gppgpag transfers to the brain, and ameliorates memory dysfunction and dendritic atrophy in alzheimer’s disease model mice |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160438/ https://www.ncbi.nlm.nih.gov/pubmed/34054554 http://dx.doi.org/10.3389/fphar.2021.680652 |
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