Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies

Qiuchen Zheng; Micheal T Kebede; Merc M Kemeh; Saadman Islam; Bethany Lee; Stuart D Bleck; Liliana A Wurfl; Noel D Lazo

doi:10.3390/molecules24122316

Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies

Molecules. 2019 Jun 22;24(12):2316. doi: 10.3390/molecules24122316.

Authors

Qiuchen Zheng¹, Micheal T Kebede², Merc M Kemeh³, Saadman Islam⁴, Bethany Lee⁵, Stuart D Bleck⁶, Liliana A Wurfl⁷, Noel D Lazo⁸

Affiliations

¹ Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USA. qzheng@clarku.edu.
² Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USA. mkebede@clarku.edu.
³ Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USA. mkemeh@clarku.edu.
⁴ Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USA. sislam@clarku.edu.
⁵ Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USA. blee@clarku.edu.
⁶ Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USA. sbleck@clarku.edu.
⁷ Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USA. lwurfl@clarku.edu.
⁸ Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USA. nlazo@clarku.edu.

Abstract

The amyloid-β (Aβ) peptide and tau protein are thought to play key neuropathogenic roles in Alzheimer's disease (AD). Both Aβ 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 Aβ and tau. Polyphenols modulate the enzymatic processing of the amyloid-β precursor protein and inhibit toxic Aβ oligomerization by enhancing the clearance of Aβ42 monomer, modulating monomer-monomer interactions and remodeling oligomers to non-toxic forms. Additionally, polyphenols modulate tau hyperphosphorylation and inhibit tau β-sheet formation. The anti-Aβ-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.

Keywords: Alzheimer′s disease; amyloid assemblies; amyloid-β self-assembly; neurofibrillary tangles; polyphenols; tau hyperphosphorylation; tau self-assembly.

Publication types

Review

MeSH terms

Amyloid beta-Peptides / chemistry
Amyloid beta-Peptides / metabolism*
Animals
Humans
Models, Molecular
Molecular Structure
Phosphorylation
Polyphenols / chemistry
Polyphenols / pharmacology*
Protein Aggregates / drug effects*
Protein Aggregation, Pathological / drug therapy
Protein Binding
Protein Multimerization / drug effects*
Structure-Activity Relationship
tau Proteins / chemistry
tau Proteins / metabolism*

Substances

Amyloid beta-Peptides
Polyphenols
Protein Aggregates
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding