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Neuroprotective Effects of Tripeptides—Epigenetic Regulators in Mouse Model of Alzheimer’s Disease

KED and EDR peptides prevent dendritic spines loss in amyloid synaptotoxicity in in vitro model of Alzheimer’s disease (AD). The objective of this paper was to study epigenetic mechanisms of EDR and KED peptides’ neuroprotective effects on neuroplasticity and dendritic spine morphology in an AD mous...

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Autores principales: Khavinson, Vladimir, Ilina, Anastasiia, Kraskovskaya, Nina, Linkova, Natalia, Kolchina, Nina, Mironova, Ekaterina, Erofeev, Alexander, Petukhov, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227791/
https://www.ncbi.nlm.nih.gov/pubmed/34071923
http://dx.doi.org/10.3390/ph14060515
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author Khavinson, Vladimir
Ilina, Anastasiia
Kraskovskaya, Nina
Linkova, Natalia
Kolchina, Nina
Mironova, Ekaterina
Erofeev, Alexander
Petukhov, Michael
author_facet Khavinson, Vladimir
Ilina, Anastasiia
Kraskovskaya, Nina
Linkova, Natalia
Kolchina, Nina
Mironova, Ekaterina
Erofeev, Alexander
Petukhov, Michael
author_sort Khavinson, Vladimir
collection PubMed
description KED and EDR peptides prevent dendritic spines loss in amyloid synaptotoxicity in in vitro model of Alzheimer’s disease (AD). The objective of this paper was to study epigenetic mechanisms of EDR and KED peptides’ neuroprotective effects on neuroplasticity and dendritic spine morphology in an AD mouse model. Daily intraperitoneal administration of the KED peptide in 5xFAD mice from 2 to 4 months of age at a concentration of 400 μg/kg tended to increase neuroplasticity. KED and EDR peptides prevented dendritic spine loss in 5xFAD-M mice. Their action’s possible molecular mechanisms were investigated by molecular modeling and docking of peptides in dsDNA, containing all possible combinations of hexanucleotide sequences. Similar DNA sequences were found in the lowest-energy complexes of the studied peptides with DNA in the classical B-form. EDR peptide has binding sites in the promoter region of CASP3, NES, GAP43, APOE, SOD2, PPARA, PPARG, GDX1 genes. Protein products of these genes are involved in AD pathogenesis. The neuroprotective effect of EDR and KED peptides in AD can be defined by their ability to prevent dendritic spine elimination and neuroplasticity impairments at the molecular epigenetic level.
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spelling pubmed-82277912021-06-26 Neuroprotective Effects of Tripeptides—Epigenetic Regulators in Mouse Model of Alzheimer’s Disease Khavinson, Vladimir Ilina, Anastasiia Kraskovskaya, Nina Linkova, Natalia Kolchina, Nina Mironova, Ekaterina Erofeev, Alexander Petukhov, Michael Pharmaceuticals (Basel) Article KED and EDR peptides prevent dendritic spines loss in amyloid synaptotoxicity in in vitro model of Alzheimer’s disease (AD). The objective of this paper was to study epigenetic mechanisms of EDR and KED peptides’ neuroprotective effects on neuroplasticity and dendritic spine morphology in an AD mouse model. Daily intraperitoneal administration of the KED peptide in 5xFAD mice from 2 to 4 months of age at a concentration of 400 μg/kg tended to increase neuroplasticity. KED and EDR peptides prevented dendritic spine loss in 5xFAD-M mice. Their action’s possible molecular mechanisms were investigated by molecular modeling and docking of peptides in dsDNA, containing all possible combinations of hexanucleotide sequences. Similar DNA sequences were found in the lowest-energy complexes of the studied peptides with DNA in the classical B-form. EDR peptide has binding sites in the promoter region of CASP3, NES, GAP43, APOE, SOD2, PPARA, PPARG, GDX1 genes. Protein products of these genes are involved in AD pathogenesis. The neuroprotective effect of EDR and KED peptides in AD can be defined by their ability to prevent dendritic spine elimination and neuroplasticity impairments at the molecular epigenetic level. MDPI 2021-05-27 /pmc/articles/PMC8227791/ /pubmed/34071923 http://dx.doi.org/10.3390/ph14060515 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Khavinson, Vladimir
Ilina, Anastasiia
Kraskovskaya, Nina
Linkova, Natalia
Kolchina, Nina
Mironova, Ekaterina
Erofeev, Alexander
Petukhov, Michael
Neuroprotective Effects of Tripeptides—Epigenetic Regulators in Mouse Model of Alzheimer’s Disease
title Neuroprotective Effects of Tripeptides—Epigenetic Regulators in Mouse Model of Alzheimer’s Disease
title_full Neuroprotective Effects of Tripeptides—Epigenetic Regulators in Mouse Model of Alzheimer’s Disease
title_fullStr Neuroprotective Effects of Tripeptides—Epigenetic Regulators in Mouse Model of Alzheimer’s Disease
title_full_unstemmed Neuroprotective Effects of Tripeptides—Epigenetic Regulators in Mouse Model of Alzheimer’s Disease
title_short Neuroprotective Effects of Tripeptides—Epigenetic Regulators in Mouse Model of Alzheimer’s Disease
title_sort neuroprotective effects of tripeptides—epigenetic regulators in mouse model of alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227791/
https://www.ncbi.nlm.nih.gov/pubmed/34071923
http://dx.doi.org/10.3390/ph14060515
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