Peptide–Polyphenol (KLVFF/EGCG) Binary Modulators for Inhibiting Aggregation and Neurotoxicity of Amyloid-β Peptide

Alzheimer’s disease (AD) is known as a typical neurodegenerative disease, and the pathogenic hallmark is the aggregation and deposition of amyloid-β peptide (Aβ) fibrils and plaque on neuronal cells resulting in cell dysfunction and cell death. One effective approach to preventing and curing AD lies in tuning Aβ aggregation and inhibiting the neurotoxicity by using molecular modulators. Peptide breakers and antioxidants are widely used inhibitors to modulate Aβ aggregation and neurotoxicity, although less efficiency of single modulators hinders the practical application of these molecules. An integration of different molecular modulators is expected to make use of multiple interactions and modulating sites and therefore synergistically improve the capacity of modulators in inhibiting Aβ aggregation. In this work, the concept of a binary peptide–polyphenol binary modulator (Aβ-segment KLVFF and (−)-epigallocatechin-3-gallate, KLVFF/EGCG) is proposed, and the synergistic effect of the KLVFF/EGCG modulator i...