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

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• dc.contributor.author Gallego-Villarejo, Lucía
• dc.contributor.author Wallin, Cecilia
• dc.contributor.author Król, Sylwia
• dc.contributor.author Enrich-Bengoa, Jennifer
• dc.contributor.author Suades, Albert
• dc.contributor.author Aguilella-Arzo, Marcel
• dc.contributor.author Gomara, Maria J.
• dc.contributor.author Haro, Isabel
• dc.contributor.author Wärmlander, Sebastian
• dc.contributor.author Muñoz López, Francisco José, 1964-
• dc.contributor.author Gräslund, Astrid
• dc.contributor.author Perálvarez Marín, Alex
• dc.date.accessioned 2023-01-25T07:32:56Z
• dc.date.available 2023-01-25T07:32:56Z
• dc.date.issued 2022
• dc.description.abstract 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.
• dc.description.sponsorship 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Gallego-Villarejo L, Wallin C, Król S, Enrich-Bengoa J, Suades A, Aguilella-Arzo M, Gomara MJ, Haro I, Wärmlander S, Muñoz FJ, Gräslund A, Perálvarez-Marín A. Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity. Comput Struct Biotechnol J. 2022 Oct 14;20:5672-9. DOI: 10.1016/j.csbj.2022.10.014
• dc.identifier.doi http://dx.doi.org/10.1016/j.csbj.2022.10.014
• dc.identifier.issn 2001-0370
• dc.identifier.uri http://hdl.handle.net/10230/55434
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Comput Struct Biotechnol J. 2022 Oct 14;20:5672-9
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-117691RB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-120222GB-I00
• dc.rights © 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/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Alzheimer’s disease
• dc.subject.keyword Amyloid β-peptide
• dc.subject.keyword Biophysics
• dc.subject.keyword Dynorphins
• dc.subject.keyword Peptide therapy
• dc.title Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion