Inhibition of the Self-Assembly of A? and of Tau by Polyphenols: Mechanistic Studies.

ABSTRACT: The amyloid-? (A?) peptide and tau protein are thought to play key neuropathogenic roles in Alzheimer's disease (AD). Both A? and tau self-assemble to form the two major pathological hallmarks of AD: amyloid plaques and neurofibrillary tangles, respectively. In this review, we show that naturally occurring polyphenols abundant in fruits, vegetables, red wine, and tea possess the ability to target pathways associated with the formation of assemblies of A? and tau. Polyphenols modulate the enzymatic processing of the amyloid-? precursor protein and inhibit toxic A? oligomerization by enhancing the clearance of A?42 monomer, modulating monomer-monomer interactions and remodeling oligomers to non-toxic forms. Additionally, polyphenols modulate tau hyperphosphorylation and inhibit tau ?-sheet formation. The anti-A?-self-assembly and anti-tau-self-assembly effects of polyphenols increase their potential as preventive or therapeutic agents against AD, a complex disease that involves many pathological mechanisms.

SUBMITTER: Zheng Q 

PROVIDER: S-EPMC6630797 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature