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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Research Network of Computational and Structural Biotechnology
2022
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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 |
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. |
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