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Published on: May 22, 2018
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.
Abstract:
Inhibition of β-amyloid (Aβ) aggregation is an attractive therapeutic and preventive strategy for the discovery of disease-modifying agents in Alzheimer's disease (AD). Phomopsis occulta is a new, salt-tolerant fungus isolated from mangrove Pongamia pinnata (L.) Pierre. We report here the inhibitory effects of secondary metabolites from Ph. occulta on the aggregation of Aβ42. It was found that mycelia extracts (MEs) from Ph. occulta cultured with 0, 2, and 3 M NaCl exhibited inhibitory activity in an E. coli model of Aβ aggregation. A water-soluble fraction, ME0-W-F1, composed of mainly small peptides, was able to reduce aggregation of an Aβ42-EGFP fusion protein and an early onset familial mutation Aβ42E22G-mCherry fusion protein in transfected HEK293 cells. ME0-W-F1 also antagonized the cytotoxicity of Aβ42 in the neural cell line SH-SY5Y in dose-dependent manner. Moreover, SDS-PAGE and FT-IR analysis confirmed an inhibitory effect of ME0-W-F1 on the aggregation of Aβ42 in vitro. ME0-W-F1 blocked the conformational transition of Aβ42 from α-helix/random coil to β-sheet, and thereby inhibited formation of Aβ42 tetramers and high molecular weight oligomers. ME0-W-F1 and other water-soluble secondary metabolites from Ph. occulta therefore represent new candidate natural products against aggregation of Aβ42, and illustrate the potential of salt tolerant fungi from mangrove as resources for the treatment of AD and other diseases.
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.
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