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

Amyloid O-peptide (AO) misfolding into O-sheet structures triggers neurotoxicity inducing Alzheimer's disease (AD). Molecules able to reduce or to impair AO aggregation are highly relevant as possible AD treatments since they should protect against AO neurotoxicity. We have studied the effects of the interaction of dynorphins, a family of opioid neuropeptides, with AO40 the most abundant species of AO. Biophysical measurements indicate that AO40 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 AO40 aggregates when studied in human neuroblastoma cells by cell survival assays. The cross-interaction between BigDyn and AO40 provides insight into the mechanism of amyloid pathophysiology and may open up new therapy possibilities.(c) 2022 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).