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Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes

Aβ(1-42) peptide is a neurotoxic agent strongly associated with the etiology of Alzheimer’s disease (AD). Current treatments are still of very low effectiveness, and deaths from AD are increasing worldwide. Huprine-derived molecules have a high affinity towards the enzyme acetylcholinesterase (AChE)...

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Autores principales: Zambrano, Pablo, Suwalsky, Mario, Jemiola-Rzeminska, Malgorzata, Gallardo-Nelson, María José, Strzalka, Kazimierz, Muñoz-Torrero, Diego
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431064/
https://www.ncbi.nlm.nih.gov/pubmed/34502472
http://dx.doi.org/10.3390/ijms22179563
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author Zambrano, Pablo
Suwalsky, Mario
Jemiola-Rzeminska, Malgorzata
Gallardo-Nelson, María José
Strzalka, Kazimierz
Muñoz-Torrero, Diego
author_facet Zambrano, Pablo
Suwalsky, Mario
Jemiola-Rzeminska, Malgorzata
Gallardo-Nelson, María José
Strzalka, Kazimierz
Muñoz-Torrero, Diego
author_sort Zambrano, Pablo
collection PubMed
description Aβ(1-42) peptide is a neurotoxic agent strongly associated with the etiology of Alzheimer’s disease (AD). Current treatments are still of very low effectiveness, and deaths from AD are increasing worldwide. Huprine-derived molecules have a high affinity towards the enzyme acetylcholinesterase (AChE), act as potent Aβ(1-42) peptide aggregation inhibitors, and improve the behavior of experimental animals. AVCRI104P4 is a multitarget donepezil-huprine hybrid that improves short-term memory in a mouse model of AD and exerts protective effects in transgenic Caenorhabditis elegans that express Aβ(1-42) peptide. At present, there is no information about the effects of this compound on human erythrocytes. Thus, we considered it important to study its effects on the cell membrane and erythrocyte models, and to examine its protective effect against the toxic insult induced by Aβ(1-42) peptide in this cell and models. This research was developed using X-ray diffraction and differential scanning calorimetry (DSC) on molecular models of the human erythrocyte membrane constituted by lipid bilayers built of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). They correspond to phospholipids representative of those present in the external and internal monolayers, respectively, of most plasma and neuronal membranes. The effect of AVCRI104P4 on human erythrocyte morphology was studied by scanning electron microscopy (SEM). The experimental results showed a protective effect of AVCRI104P4 against the toxicity induced by Aβ(1-42) peptide in human erythrocytes and molecular models.
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spelling pubmed-84310642021-09-11 Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes Zambrano, Pablo Suwalsky, Mario Jemiola-Rzeminska, Malgorzata Gallardo-Nelson, María José Strzalka, Kazimierz Muñoz-Torrero, Diego Int J Mol Sci Article Aβ(1-42) peptide is a neurotoxic agent strongly associated with the etiology of Alzheimer’s disease (AD). Current treatments are still of very low effectiveness, and deaths from AD are increasing worldwide. Huprine-derived molecules have a high affinity towards the enzyme acetylcholinesterase (AChE), act as potent Aβ(1-42) peptide aggregation inhibitors, and improve the behavior of experimental animals. AVCRI104P4 is a multitarget donepezil-huprine hybrid that improves short-term memory in a mouse model of AD and exerts protective effects in transgenic Caenorhabditis elegans that express Aβ(1-42) peptide. At present, there is no information about the effects of this compound on human erythrocytes. Thus, we considered it important to study its effects on the cell membrane and erythrocyte models, and to examine its protective effect against the toxic insult induced by Aβ(1-42) peptide in this cell and models. This research was developed using X-ray diffraction and differential scanning calorimetry (DSC) on molecular models of the human erythrocyte membrane constituted by lipid bilayers built of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). They correspond to phospholipids representative of those present in the external and internal monolayers, respectively, of most plasma and neuronal membranes. The effect of AVCRI104P4 on human erythrocyte morphology was studied by scanning electron microscopy (SEM). The experimental results showed a protective effect of AVCRI104P4 against the toxicity induced by Aβ(1-42) peptide in human erythrocytes and molecular models. MDPI 2021-09-03 /pmc/articles/PMC8431064/ /pubmed/34502472 http://dx.doi.org/10.3390/ijms22179563 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
Zambrano, Pablo
Suwalsky, Mario
Jemiola-Rzeminska, Malgorzata
Gallardo-Nelson, María José
Strzalka, Kazimierz
Muñoz-Torrero, Diego
Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes
title Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes
title_full Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes
title_fullStr Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes
title_full_unstemmed Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes
title_short Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes
title_sort protective role of a donepezil-huprine hybrid against the β-amyloid (1-42) effect on human erythrocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431064/
https://www.ncbi.nlm.nih.gov/pubmed/34502472
http://dx.doi.org/10.3390/ijms22179563
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