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 (...

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Authors: Zambrano, Pablo, Suwalsky, Mario, Jemiola-Rzeminska, Malgorzata, Gallardo-Nelson, María José, Strzalka, Kazimierz, Muñoz-Torrero López-Ibarra, Diego
Format: article
Status:Published version
Publication Date:2021
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/179919
Online Access:https://hdl.handle.net/2445/179919
Access Level:Open access
Keyword:Malaltia d'Alzheimer
Malalties neurodegeneratives
Escorça cerebral
Pèptids
Alzheimer's disease
Neurodegenerative Diseases
Cerebral cortex
Peptides
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spelling Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human ErythrocytesZambrano, PabloSuwalsky, MarioJemiola-Rzeminska, MalgorzataGallardo-Nelson, María JoséStrzalka, KazimierzMuñoz-Torrero López-Ibarra, DiegoMalaltia d'AlzheimerMalalties neurodegenerativesEscorça cerebralPèptidsAlzheimer's diseaseNeurodegenerative DiseasesCerebral cortexPeptidesAβ(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.MDPI2021202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/179919Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/ijms22179563International Journal of Molecular Sciences, 2021, vol. 22, num. 17, p. 9563https://doi.org/10.3390/ijms22179563cc-by (c) Zambrano, Pablo et al., 2021https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1799192026-05-29T05:05:01Z
dc.title.none.fl_str_mv 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
spellingShingle Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes
Zambrano, Pablo
Malaltia d'Alzheimer
Malalties neurodegeneratives
Escorça cerebral
Pèptids
Alzheimer's disease
Neurodegenerative Diseases
Cerebral cortex
Peptides
title_short 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_sort Protective Role of a Donepezil-Huprine Hybrid against the β-Amyloid (1-42) Effect on Human Erythrocytes
dc.creator.none.fl_str_mv Zambrano, Pablo
Suwalsky, Mario
Jemiola-Rzeminska, Malgorzata
Gallardo-Nelson, María José
Strzalka, Kazimierz
Muñoz-Torrero López-Ibarra, Diego
author Zambrano, Pablo
author_facet Zambrano, Pablo
Suwalsky, Mario
Jemiola-Rzeminska, Malgorzata
Gallardo-Nelson, María José
Strzalka, Kazimierz
Muñoz-Torrero López-Ibarra, Diego
author_role author
author2 Suwalsky, Mario
Jemiola-Rzeminska, Malgorzata
Gallardo-Nelson, María José
Strzalka, Kazimierz
Muñoz-Torrero López-Ibarra, Diego
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Malaltia d'Alzheimer
Malalties neurodegeneratives
Escorça cerebral
Pèptids
Alzheimer's disease
Neurodegenerative Diseases
Cerebral cortex
Peptides
topic Malaltia d'Alzheimer
Malalties neurodegeneratives
Escorça cerebral
Pèptids
Alzheimer's disease
Neurodegenerative Diseases
Cerebral cortex
Peptides
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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/179919
url https://hdl.handle.net/2445/179919
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ijms22179563
International Journal of Molecular Sciences, 2021, vol. 22, num. 17, p. 9563
https://doi.org/10.3390/ijms22179563
dc.rights.none.fl_str_mv cc-by (c) Zambrano, Pablo et al., 2021
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Zambrano, Pablo et al., 2021
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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