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

Gallego-Villarejo, Lucía; Wallin, Cecilia; Król, Sylwia; Enrich-Bengoa, Jennifer; Suades, Albert; Aguilella-Arzo, Marcel; Gomara, Maria J.; Haro, Isabel; Wärmlander, Sebastian; Muñoz López, Francisco José, 1964-; Gräslund, Astrid; Perálvarez Marín, Alex

doi:http://dx.doi.org/10.1016/j.csbj.2022.10.014

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

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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. 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

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.