Cargando…

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 of th...

Descripción completa

Detalles Bibliográficos
Autores principales: Gallego-Villarejo, Lucía, Wallin, Cecilia, Król, Sylwia, Enrich-Bengoa, Jennifer, Suades, Albert, Aguilella-Arzo, Marcel, Gomara, María José, Haro, Isabel, Wärmlander, Sebastian, Muñoz, Francisco J., Gräslund, Astrid, Perálvarez-Marín, Alex
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Research Network of Computational and Structural Biotechnology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582793/
https://www.ncbi.nlm.nih.gov/pubmed/36284704
http://dx.doi.org/10.1016/j.csbj.2022.10.014
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(40) the most abundant species of Aβ. Biophysical measurements indicate that Aβ(40) 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(40) aggregates when studied in human neuroblastoma cells by cell survival assays. The cross-interaction between BigDyn and Aβ(40) provides insight into the mechanism of amyloid pathophysiology and may open up new therapy possibilities.