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 effects...

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Detalles Bibliográficos
Autores: Gallego-Villarejo, Lucía|||0000-0002-4219-8997, Wallin, C., Król, S., Enrich-Bengoa, Jennifer|||0000-0002-0840-4005, Suades, Albert, Aguilella-Arzo, Marcel|||0000-0002-2831-455X, Gómara Elena, María José, Haro, Immaculada, Wärmlander, S., Muñoz, Francisco J., Gräslund, A., Peralvarez-Marin, Alex|||0000-0002-3457-0875
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:292093
Acceso en línea:https://ddd.uab.cat/record/292093
https://dx.doi.org/urn:doi:10.1016/j.csbj.2022.10.014
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
Amyloid β-peptide
Biophysics
Dynorphins
Peptide therapy
Descripción
Sumario: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 Aβ the most abundant species of Aβ. Biophysical measurements indicate that Aβ 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 Aβ aggregates when studied in human neuroblastoma cells by cell survival assays. The cross-interaction between BigDyn and Aβ provides insight into the mechanism of amyloid pathophysiology and may open up new therapy possibilities.