amyloid-beta-protein-(17-42) and Cognitive-Dysfunction

Fast green FCF (FGF) is often used in foods, pharmaceuticals, and cosmetics. However, little is known about the interactions of FGF with amyloid-β protein (Aβ) associated with Alzheimer's disease. In this study, the inhibitory effects of FGF on Aβ fibrillogenesis, the disruption of preformed Aβ fibrils, the reduction of Aβ-induced cytotoxicity, and the attenuation of Aβ-induced learning and memory impairments in mice were investigated. FGF significantly inhibited Aβ fibrillogenesis and disintegrated the mature fibrils as evidenced by thioflavin T fluorescence and atomic force microscopy studies. Co-incubation of Aβ with FGF greatly reduced Aβ-induced cytotoxicity in vitro. Moreover, FGF showed a protective effect against cognitive impairment in Aβ-treated mice. Molecular dynamics simulations further showed that FGF could synergistically interact with the Aβ17-42 pentamer via electrostatic interactions, hydrogen bonds and π-π interactions, which reduced the β-sheet content, and disordered random coils and bend structures of the Aβ17-42 pentamer. This study offers a comprehensive understanding of the inhibitory effects of FGF against Aβ neurotoxicity, which is critical for the search of effective food additives that can combat amyloid-associated disease.

Topics: Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Animals; Cognitive Dysfunction; Exploratory Behavior; Food Additives; Humans; Hydrogen Bonding; Lissamine Green Dyes; Mice; Microscopy, Atomic Force; Models, Molecular; Molecular Dynamics Simulation; Morris Water Maze Test; Neuroprotective Agents; Peptide Fragments; Protein Aggregation, Pathological; Protein Structure, Secondary; Random Allocation; Static Electricity