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

ABSTRACT: Aggregation of amyloid ?42 (A?42) is one of the hallmarks of Alzheimer's disease (AD). There are numerous naturally occurring products that suppress the aggregation of A?42, 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 A?42 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 A?42 through flavonoid autoxidation; (2) non-catechol-type flavonoids with planarity due to ?,?-unsaturated carbonyl groups that can interact with the intermolecular ?-sheet region in A?42 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 A?42 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.

SUBMITTER: Murakami K 

PROVIDER: S-EPMC6600243 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature