Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity

Amyloid β-peptide (Aβ) misfolding into β-sheet structures triggers neurotoxicity inducing Alzheimer's disease (AD). Molecules able to reduce or to impair Aβ aggregation are highly relevant as possible AD treatments since they should protect against Aβ neurotoxicity. We have studied the effe...

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Detalles Bibliográficos
Autores: Gallego-Villarejo, Lucía, Wallin, Cecilia, Król, Sylwia, Enrich-Bengoa, Jennifer, Suades, Albert, Aguilella-Arzo, Marcel, Gomara, Maria J., Haro, Isabel, Wärmlander, Sebastian, Muñoz López, Francisco José, 1964-, Gräslund, Astrid, Perálvarez Marín, Alex
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/55434
Acceso en línea:http://hdl.handle.net/10230/55434
http://dx.doi.org/10.1016/j.csbj.2022.10.014
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease
Amyloid β-peptide
Biophysics
Dynorphins
Peptide therapy
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spelling Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicityGallego-Villarejo, LucíaWallin, CeciliaKról, SylwiaEnrich-Bengoa, JenniferSuades, AlbertAguilella-Arzo, MarcelGomara, Maria J.Haro, IsabelWärmlander, SebastianMuñoz López, Francisco José, 1964-Gräslund, AstridPerálvarez Marín, AlexAlzheimer’s diseaseAmyloid β-peptideBiophysicsDynorphinsPeptide therapyAmyloid β-peptide (Aβ) misfolding into β-sheet structures triggers neurotoxicity inducing Alzheimer's disease (AD). Molecules able to reduce or to impair Aβ aggregation are highly relevant as possible AD treatments since they should protect against Aβ neurotoxicity. We have studied the effects of the interaction of dynorphins, a family of opioid neuropeptides, with Aβ40 the most abundant species of Aβ. Biophysical measurements indicate that Aβ40 interacts with Big Dynorphin (BigDyn), lowering the amount of hydrophobic aggregates, and slowing down the aggregation kinetics. As expected, we found that BigDyn protects against Aβ40 aggregates when studied in human neuroblastoma cells by cell survival assays. The cross-interaction between BigDyn and Aβ40 provides insight into the mechanism of amyloid pathophysiology and may open up new therapy possibilities.This work was supported by the Spanish Ministry of Science and Innovation and Agencia Estatal de Investigación through grant MCIN/AEI/ https://doi.org/10.13039/501100011033 (projects 2019-108434GB-I00 to M.A.-A., PID2020-117691RB-I00 to F.J.M., and PID2020-120222GB-I00 to A.P.-M.), Generalitat Valenciana (project AICO/2020/066 to M.A-A.), FEDER Funds and by the “María de Maeztu Programme” for Units of Excellence in R&D (award CEX2018-000792-M). A.G. was supported by grants from the Swedish Research Council.Elsevier202320232022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/55434http://dx.doi.org/10.1016/j.csbj.2022.10.014reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésComput Struct Biotechnol J. 2022 Oct 14;20:5672-9info:eu-repo/grantAgreement/ES/2PE/PID2020-117691RB-I00info:eu-repo/grantAgreement/ES/2PE/PID2020-120222GB-I00© 2022 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/554342026-05-29T05:05:01Z
dc.title.none.fl_str_mv Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity
title Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity
spellingShingle Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity
Gallego-Villarejo, Lucía
Alzheimer’s disease
Amyloid β-peptide
Biophysics
Dynorphins
Peptide therapy
title_short Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity
title_full Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity
title_fullStr Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity
title_full_unstemmed Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity
title_sort Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity
dc.creator.none.fl_str_mv Gallego-Villarejo, Lucía
Wallin, Cecilia
Król, Sylwia
Enrich-Bengoa, Jennifer
Suades, Albert
Aguilella-Arzo, Marcel
Gomara, Maria J.
Haro, Isabel
Wärmlander, Sebastian
Muñoz López, Francisco José, 1964-
Gräslund, Astrid
Perálvarez Marín, Alex
author Gallego-Villarejo, Lucía
author_facet Gallego-Villarejo, Lucía
Wallin, Cecilia
Król, Sylwia
Enrich-Bengoa, Jennifer
Suades, Albert
Aguilella-Arzo, Marcel
Gomara, Maria J.
Haro, Isabel
Wärmlander, Sebastian
Muñoz López, Francisco José, 1964-
Gräslund, Astrid
Perálvarez Marín, Alex
author_role author
author2 Wallin, Cecilia
Król, Sylwia
Enrich-Bengoa, Jennifer
Suades, Albert
Aguilella-Arzo, Marcel
Gomara, Maria J.
Haro, Isabel
Wärmlander, Sebastian
Muñoz López, Francisco José, 1964-
Gräslund, Astrid
Perálvarez Marín, Alex
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer’s disease
Amyloid β-peptide
Biophysics
Dynorphins
Peptide therapy
topic Alzheimer’s disease
Amyloid β-peptide
Biophysics
Dynorphins
Peptide therapy
description Amyloid β-peptide (Aβ) misfolding into β-sheet structures triggers neurotoxicity inducing Alzheimer's disease (AD). Molecules able to reduce or to impair Aβ aggregation are highly relevant as possible AD treatments since they should protect against Aβ neurotoxicity. We have studied the effects of the interaction of dynorphins, a family of opioid neuropeptides, with Aβ40 the most abundant species of Aβ. Biophysical measurements indicate that Aβ40 interacts with Big Dynorphin (BigDyn), lowering the amount of hydrophobic aggregates, and slowing down the aggregation kinetics. As expected, we found that BigDyn protects against Aβ40 aggregates when studied in human neuroblastoma cells by cell survival assays. The cross-interaction between BigDyn and Aβ40 provides insight into the mechanism of amyloid pathophysiology and may open up new therapy possibilities.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
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 http://hdl.handle.net/10230/55434
http://dx.doi.org/10.1016/j.csbj.2022.10.014
url http://hdl.handle.net/10230/55434
http://dx.doi.org/10.1016/j.csbj.2022.10.014
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Comput Struct Biotechnol J. 2022 Oct 14;20:5672-9
info:eu-repo/grantAgreement/ES/2PE/PID2020-117691RB-I00
info:eu-repo/grantAgreement/ES/2PE/PID2020-120222GB-I00
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv 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 15,812429

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