Three Structural Features of Functional Food Components and Herbal Medicine with Amyloid 42 Anti-Aggregation Properties

Aggregation of amyloid 42 (A42) is one of the hallmarks of Alzheimer's disease (AD). There are numerous naturally occurring products that suppress the aggregation of A42, but the underlying mechanisms remain to be elucidated. Based on NMR and MS spectroscopic analysis, we propose three structural characteristics found in natural products required for the suppressive activity against A42 aggregation (i.e., oligomerization by targeting specific amino acid residues on this protein). These characteristics include (1) catechol-type flavonoids that can form Michael adducts with the side chains of Lys16 and 28 in monomeric A42 through flavonoid autoxidation; (2) non-catechol-type flavonoids with planarity due to ,-unsaturated carbonyl groups that can interact with the intermolecular -sheet region in A42 aggregates, especially aromatic rings such as those of Phe19 and 20; and (3) carboxy acid derivatives with triterpenoid or anthraquinoid that can generate a salt bridge with basic amino acid residues such as Lys16 and 28 in the A42 dimer or trimer. Here, we summarize the recent body of knowledge concerning amyloidogenic inhibitors, particularly in functional food components and Kampo medicine, and discuss their application in the treatment and prevention of AD.