Effects of secondary metabolite extract from Phomopsis occulta on β-amyloid aggregation

Haiqiang Wu1, Fang Zhang1, Neil Williamson2

  • 1College of Life Sciences, Shenzhen University, Shenzhen, China.

Plos One
|October 3, 2014
PubMed

Insights

Secondary metabolites from the salt-tolerant fungus Phomopsis occulta inhibit beta-amyloid (Aβ) aggregation, a key process in Alzheimer's disease (AD). These compounds, particularly a peptide-rich fraction, show potential as natural therapeutic agents against Aβ42 toxicity.

Area of Science:

  • Biochemistry
  • Neuroscience
  • Marine Biotechnology

Background:

  • Alzheimer's disease (AD) is characterized by the aggregation of beta-amyloid (Aβ) peptides.
  • Inhibiting Aβ aggregation is a key therapeutic strategy for AD.
  • Mangrove-derived fungi are a potential source of novel bioactive compounds.

Purpose of the Study:

  • To investigate the potential of secondary metabolites from the salt-tolerant fungus Phomopsis occulta to inhibit Aβ42 aggregation.
  • To identify specific fractions with anti-amyloidogenic properties.
  • To evaluate the therapeutic potential of these compounds for Alzheimer's disease.

Main Methods:

  • Culturing Phomopsis occulta under varying salt concentrations (0, 2, 3 M NaCl).
  • Assessing Aβ aggregation inhibition using an E. coli model and fusion proteins (Aβ42-EGFP, Aβ42E22G-mCherry) in HEK293 cells.
  • Evaluating cytotoxicity in SH-SY5Y neural cells.
  • Analyzing the effect on Aβ42 conformation and oligomerization using SDS-PAGE and FT-IR.

Main Results:

  • Mycelia extracts from Ph. occulta showed inhibitory activity against Aβ aggregation.
  • A water-soluble fraction (ME0-W-F1), rich in small peptides, reduced Aβ42 and mutant Aβ42 aggregation in cellular models.
  • ME0-W-F1 demonstrated dose-dependent antagonism of Aβ42-induced cytotoxicity in neural cells.
  • In vitro studies confirmed ME0-W-F1 inhibited Aβ42 aggregation by blocking the transition to β-sheet structure and preventing oligomer formation.

Conclusions:

  • Phomopsis occulta produces secondary metabolites with significant inhibitory effects on Aβ42 aggregation.
  • The peptide-rich fraction ME0-W-F1 is a promising candidate for developing natural anti-AD agents.
  • Salt-tolerant mangrove fungi represent a valuable resource for discovering novel therapeutic compounds for neurodegenerative diseases like AD.