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

ABSTRACT: Inhibition of ?-amyloid (A?) 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 A?42. 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 A? aggregation. A water-soluble fraction, ME0-W-F1, composed of mainly small peptides, was able to reduce aggregation of an A?42-EGFP fusion protein and an early onset familial mutation A?42E22G-mCherry fusion protein in transfected HEK293 cells. ME0-W-F1 also antagonized the cytotoxicity of A?42 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 A?42 in vitro. ME0-W-F1 blocked the conformational transition of A?42 from ?-helix/random coil to ?-sheet, and thereby inhibited formation of A?42 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 A?42, and illustrate the potential of salt tolerant fungi from mangrove as resources for the treatment of AD and other diseases.

SUBMITTER: Wu H 

PROVIDER: S-EPMC4183696 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature