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

作者：Gonzalez Ramirez Mariela; Gavilan Javiera; Silva Grecchi Tiare; Cajas Madriaga Daniel; Trivino Sergio; Becerra Jose; Saez Orellana Francisco; Perez Claudia^*; Fuentealba Jorge^*

来源：Journal of Alzheimer's Disease, 2018, 61(4): 1463-1475.

DOI：10.3233/JAD-170958

• Alzheimer's disease
• A beta peptide inhibitor
• benzofuran
• fomannoxin

Alzheimer's disease (AD) is characterized by amyloid plaques that form due to an increase in amyloid-beta peptide (A beta) aggregation. One strategy in the search of new treatments for AD focuses on compounds that decrease A beta accumulation. Compounds containing a benzofuran ring have been described to play an important role in decreasing A beta-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 A beta 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 concentrationdependent effect on the A beta-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 A beta-induced decrease in intracellular Ca2+ transients was prevented when Fx (10(-6) M) was co-incubated with A beta (5x10(-6) M). The results suggest a potent neuroprotective effect of this naturally occurring benzofuran against A beta 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 A beta peptide neurotoxicity.

• 出版日期2018