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
UR - https://www.scopus.com/pages/publications/85140094234
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 -
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