title: Effects of secondary metabolite extract from Phomopsis occulta on β-amyloid aggregation.
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.
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Haiqiang
authors.initials: H
authors.lastname: Wu
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Williamson
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom; College of Pharmacy, Guilin Medical University, Guilin, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jian
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Liao
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Zeqiu
authors.initials: Z
authors.lastname: Liang
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, China.
authors.forename: Linkun
authors.initials: L
authors.lastname: An
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Tunnacliffe
authors.affiliation: College of Life Sciences, Shenzhen University, Shenzhen, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D005658:Fungi / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D066329:Protein Aggregates / Q000187:drug effects*; D017433:Protein Structure, Secondary / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D001688:Biological Products; D010446:Peptide Fragments; D010455:Peptides; D066329:Protein Aggregates; C075222:amyloid beta-protein (1-42)