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

Lucía Gallego-Villarejo; Cecilia Wallin; Sylwia Król; Jennifer Enrich-Bengoa; Albert Suades; Marcel Aguilella-Arzo; María José Gomara; Isabel Haro; Sebastian Wärmlander; Francisco J. Muñoz; Astrid Gräslund; Alex Perálvarez-Marín

doi:10.1016/j.csbj.2022.10.014

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

Lucía Gallego-Villarejo, Cecilia Wallin, Sylwia Król, Jennifer Enrich-Bengoa, Albert Suades, Marcel Aguilella-Arzo, María José Gomara, Isabel Haro, Sebastian Wärmlander, Francisco J. Muñoz, Astrid Gräslund, Alex Perálvarez-Marín^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

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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.

Original language	English
Pages (from-to)	5672-5679
Number of pages	8
Journal	Computational and Structural Biotechnology Journal
Volume	20
DOIs	https://doi.org/10.1016/j.csbj.2022.10.014
Publication status	Published - Jan 2022

Keywords

Alzheimer's disease
Amyloid β-peptide
Biophysics
Dynorphins
Peptide therapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.csbj.2022.10.014

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Gallego-Villarejo, L., Wallin, C., Król, S., Enrich-Bengoa, J., Suades, A., Aguilella-Arzo, M., Gomara, M. J., Haro, I., Wärmlander, S., Muñoz, F. J., Gräslund, A., & Perálvarez-Marín, A. (2022). Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity. Computational and Structural Biotechnology Journal, 20, 5672-5679. https://doi.org/10.1016/j.csbj.2022.10.014

@article{e6f9e95606b94d76b2cb2790f140b711,

title = "Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity",

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.",

keywords = "Alzheimer's disease, Amyloid β-peptide, Biophysics, Dynorphins, Peptide therapy",

author = "Luc{\'i}a Gallego-Villarejo and Cecilia Wallin and Sylwia Kr{\'o}l and Jennifer Enrich-Bengoa and Albert Suades and Marcel Aguilella-Arzo and Gomara, {Mar{\'i}a Jos{\'e}} and Isabel Haro and Sebastian W{\"a}rmlander and Mu{\~n}oz, {Francisco J.} and Astrid Gr{\"a}slund and Alex Per{\'a}lvarez-Mar{\'i}n",

note = "Funding Information: This work was supported by the Spanish Ministry of Science and Innovation and Agencia Estatal de Investigaci{\'o}n 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 “Mar{\'i}a 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. Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = jan,

doi = "10.1016/j.csbj.2022.10.014",

language = "English",

volume = "20",

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journal = "Computational and Structural Biotechnology Journal",

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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 2022, 'Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity', Computational and Structural Biotechnology Journal, vol. 20, pp. 5672-5679. https://doi.org/10.1016/j.csbj.2022.10.014

TY - JOUR

T1 - Big dynorphin is a neuroprotector scaffold against amyloid β-peptide aggregation and cell toxicity

AU - Gallego-Villarejo, Lucía

AU - Wallin, Cecilia

AU - Król, Sylwia

AU - Enrich-Bengoa, Jennifer

AU - Suades, Albert

AU - Aguilella-Arzo, Marcel

AU - Gomara, María José

AU - Haro, Isabel

AU - Wärmlander, Sebastian

AU - Muñoz, Francisco J.

AU - Gräslund, Astrid

AU - Perálvarez-Marín, Alex

N1 - Funding Information: 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. Publisher Copyright: © 2022

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Amyloid β-peptide

KW - Biophysics

KW - Dynorphins

KW - Peptide therapy

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U2 - 10.1016/j.csbj.2022.10.014

DO - 10.1016/j.csbj.2022.10.014

M3 - Article

C2 - 36284704

AN - SCOPUS:85140094234

SN - 2001-0370

VL - 20

SP - 5672

EP - 5679

JO - Computational and Structural Biotechnology Journal

JF - Computational and Structural Biotechnology Journal

ER -

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

Abstract

Keywords

UN SDGs

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