%0 Journal Article %J J Alzheimers Dis %D 2023 %T Neuroprotective Properties of Eudesmin on a Cellular Model of Amyloid-β Peptide Toxicity. %A Castillo, Carolina %A Bravo-Arrepol, Gastón %A Wendt, Aline %A Saez-Orellana, Francisco %A Millar, Camila %A Burgos, Carlos F %A Gavilán, Javiera %A Pacheco, Carla %A Ahumada-Rudolph, Ramón %A Napiórkowska, Mariola %A Pérez, Claudia %A Becerra, José %A Fuentealba, Jorge %A Cabrera-Pardo, Jaime R %K Alzheimer Disease %K Amyloid beta-Peptides %K Animals %K Lignans %K Mice %K Neuroprotective Agents %K PC12 Cells %K Rats %X

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-β peptide (Aβ) accumulation, where the soluble oligomers of Aβ (AβOs) 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 AβOs 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 AβOs.

RESULTS: In primary cultures from mouse hippocampus, Eu preserved the synaptic structure against AβOs toxicity, maintaining stable levels of the presynaptic protein SV2 at the same concentration. Eu also averted synapsis failure from the AβOs toxicity by sustaining the frequencies of cytosolic Ca2+ transients. Finally, we found that Eu (30 nM) interacts with the Aβ aggregation process inducing a decrease in AβOs toxicity, suggesting an alternative mechanism to explain the neuroprotective activity of Eu.

CONCLUSION: We believe that Eu represents a novel lead that reduces the Aβ toxicity, opening new research venues for lignans as neuroprotective agents.

%B J Alzheimers Dis %V 94 %P S97-S108 %8 2023 %G eng %N s1 %R 10.3233/JAD-220935 %0 Journal Article %J J Alzheimers Dis %D 2018 %T A Natural Benzofuran from the Patagonic Aleurodiscus vitellinus Fungus has Potent Neuroprotective Properties on a Cellular Model of Amyloid-β Peptide Toxicity. %A González-Ramírez, Mariela %A Gavilán, Javiera %A Silva-Grecchi, Tiare %A Cajas-Madriaga, Daniel %A Triviño, Sergio %A Becerra, José %A Saez-Orellana, Francisco %A Pérez, Claudia %A Fuentealba, Jorge %K Alzheimer Disease %K Amyloid beta-Peptides %K Animals %K Basidiomycota %K Benzofurans %K Cell Survival %K Hippocampus %K Neurons %K Neuroprotective Agents %K PC12 Cells %K Plaque, Amyloid %K Rats %X

Alzheimer's disease (AD) is characterized by amyloid plaques that form due to an increase in amyloid-β peptide (Aβ) aggregation. One strategy in the search of new treatments for AD focuses on compounds that decrease Aβ accumulation. Compounds containing a benzofuran ring have been described to play an important role in decreasing Aβ-induced toxicity; however, only synthetic benzofurans have been tested thus far. The aim of the present study was to examine the in vitro neuroprotective properties of fomannoxin (Fx), a natural benzofuran isolated from cultures of the Andean-Patagonian fungi Aleurodiscus vitellinus, and evaluate its effect on Aβ peptide. We tested the effect of Fx at a wide concentration range (10-11-10-4 M) in PC-12 cells, and found the compound did not alter cellular viability. Fx also showed a concentration-dependent effect on the Aβ-induced toxicity in PC12 cells, showing viability above 100% at 10-6 M. We then measured the effect of Fx (10-7-10-5 M) on the frequency of cytosolic Ca2+ transients in rat hippocampal neurons at both acute and chronic (24 h) times. Acute incubation with Fx increased the frequency of cytosolic Ca2+ transients to values around 200%, whereas chronic incubation with Fx increased the frequency of Ca2+ transients. Finally, the Aβ-induced decrease in intracellular Ca2+ transients was prevented when Fx (10-6 M) was co-incubated with Aβ (5×10-6 M). The results suggest a potent neuroprotective effect of this naturally occurring benzofuran against Aβ peptide toxicity that could be mediated by an interference with it binding to plasma membrane, and lead Fx as new chemical entity to develop pharmacological tools against Aβ peptide neurotoxicity.

%B J Alzheimers Dis %V 61 %P 1463-1475 %8 2018 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/29376877?dopt=Abstract %R 10.3233/JAD-170958