Interaction between polyphenols and amyloids: from the view of prevention of protein misfolding disorders related diseases

Abstract

Amyloid is the term usually used to describe a particular type of elongated, unbranched protein fibril with cross-<i>β</i>-sheet characteristics, formed through the ordered aggregation of peptides or denatured proteins. Amyloids show high association with many severe neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases. Unfortunately, there are still no effective medical treatments to cure these neurodegenerative diseases, including the failure of pharmaceutical approaches with amyloids as the targets. Polyphenols, the major phytochemicals in fruits, vegetables, tea and coffee have many beneficial functional properties, such as antioxidant, antimicrobial and anticancer properties. Polyphenols can interact with proteins through non-covalent interactions, including hydrophobic interaction, hydrogen bonding and electrostatic interaction. Polyphenols can also covalently interact with proteins mainly via the interaction between quinones, the oxidized products of polyphenols, and the nucleophilic residues (thiol, amino, guanidine, or imidazole) in protein side chains or peptides. Evidence from previous studies have indicated that polyphenols could reduce amyloid-formation via inhibiting fibril aggregation or steering oligomer formation into unstructured, nontoxic pathways. This effect was realized mainly through: (1) preventing conformational changes of precursor native proteins into amyloidogenic forms, (2) inhibiting the conversion of amyloidogenic precursors to amyloid fibrils, or (3) disrupting preformed fibrils meanwhile destructing the aggregation conditions. These findings imply that polyphenols could play a vital role in inhibiting protein misfolding, which might be useful for the prevention of various neurodegenerative diseases.