Neuroprotective Properties of Eudesmin on a Cellular Model of Amyloid-beta Peptide Toxicity

Castillo, Carolina; Bravo-Arrepol, Gaston; Wendt, Aline; Saez-Orellana, Francisco; Millar, Camila; Burgos, Carlos F.; Gavilan, Javiera; Pacheco, Carla; Ahumada-Rudolph, Ramon; Napiorkowska, Mariola; Perez, Claudia; Becerra, Jose; Fuentealba, Jorge; Cabrera-Pardo, Jaime R.


Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and memory loss. One of the hallmarks in AD is amyloid-beta peptide (A beta) accumulation, where the soluble oligomers of A beta (A beta Os) are the most toxic species, deteriorating the synaptic function, membrane integrity, and neuronal structures, which ultimately lead to apoptosis. Currently, there are no drugs to arrest AD progression, and current scientific efforts are focused on searching for novel leads to control this disease. Lignans are compounds extracted from conifers and have several medicinal properties. Eudesmin (Eu) is an extractable lignan from the wood of Araucaria araucana, a native tree from Chile. This metabolite has shown a range of biological properties, including the ability to control inflammation and antibacterial effects. Objective: In this study, the neuroprotective abilities of Eu on synaptic failure induced by A beta Os were analyzed. Methods: Using neuronal models, PC12 cells, and in silico simulations we evaluated the neuroprotective effect of Eu (30 nM) against the toxicity induced by A beta Os. Results: In primary cultures from mouse hippocampus, Eu preserved the synaptic structure against A beta Os toxicity, maintaining stable levels of the presynaptic protein SV2 at the same concentration. Eu also averted synapsis failure from the A beta Os toxicity by sustaining the frequencies of cytosolic Ca2+ transients. Finally, we found that Eu (30 nM) interacts with the A beta aggregation process inducing a decrease in A beta Os toxicity, suggesting an alternative mechanism to explain the neuroprotective activity of Eu. Conclusion: We believe that Eu represents a novel lead that reduces the A beta toxicity, opening new research venues for lignans as neuroprotective agents.

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Título según WOS: ID WOS:001045024100008 Not found in local WOS DB
Volumen: 94
Editorial: IOS Press
Fecha de publicación: 2023
Página de inicio: S97
Página final: S108


Notas: ISI