Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USA.
Molecules. 2019 Jun 22;24(12):2316. doi: 10.3390/molecules24122316.
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.
淀粉样蛋白-β（Aβ）肽和tau 蛋白被认为在阿尔茨海默病（AD）中发挥关键的神经致病作用。Aβ和tau 自身组装分别形成 AD 的两个主要病理标志物：淀粉样斑块和神经原纤维缠结。在这篇综述中，我们表明，水果、蔬菜、红酒和茶中丰富的天然多酚具有靶向与 Aβ和 tau 组装形成相关途径的能力。多酚通过增强 Aβ42 单体的清除、调节单体-单体相互作用和重塑低聚物为无毒形式，来调节淀粉样前体蛋白的酶加工，并抑制有毒的 Aβ 寡聚体的形成。此外，多酚还调节 tau 过度磷酸化并抑制 tau β-折叠的形成。多酚的抗 Aβ 自组装和抗 tau 自组装作用增加了它们作为预防或治疗 AD 的潜在用途，AD 是一种涉及多种病理机制的复杂疾病。
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