A Natural Benzofuran from the Patagonic Aleurodiscus vitellinus Fungus has Potent Neuroprotective Properties on a Cellular Model of Amyloid-β Peptide Toxicity.

Abstract

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.

• Authors: Mariela González-Ramírez, Javiera Gavilán, Tiare Silva-Grecchi, Daniel Cajas-Madriaga, Sergio Triviño, José Becerra, Francisco Saez-Orellana, Claudia Pérez, Jorge Fuentealba
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 61 Issue 4 Pg. 1463-1475 ( 2018) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 29376877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Benzofurans
• Neuroprotective Agents

Topics

• Alzheimer Disease (drug therapy)
• Amyloid beta-Peptides (toxicity)
• Animals
• Basidiomycota (chemistry)
• Benzofurans (chemistry, isolation & purification, pharmacology)
• Cell Survival (drug effects)
• Hippocampus (pathology)
• Neurons (drug effects)
• Neuroprotective Agents (chemistry, isolation & purification, pharmacology)
• PC12 Cells
• Plaque, Amyloid (drug therapy)
• Rats