Alzheimer's disease (AD) is the most common age-related
neurodegenerative disorder, responsible for nearly two-thirds of all
dementia cases. In this review, we report the potential AD treatment strategies focusing on natural
polyphenol molecules (green chemistry) and more specifically on the inhibition of
polyphenol-induced
amyloid aggregation/disaggregation pathways: in bulk and on biosurfaces. We discuss how these pathways can potentially alter the structure at the early stages of AD, hence delaying the aggregation of
amyloid-β (Aβ) and tau. We also discuss multidisciplinary approaches, combining experimental and modelling methods, that can better characterize the biochemical and biophysical interactions between
proteins and phenolic
ligands. In addition to the surface-induced aggregation, which can occur on surfaces where
protein can interact with other
proteins and
polyphenols, we suggest a new concept referred as "confinement stability". Here, on the contrary, the adsorption of Aβ and tau on biosurfaces other than Aβ- and tau-fibrils, e.g., red blood cells, can lead to confinement stability that minimizes the aggregation of Aβ and tau. Overall, these mechanisms may participate directly or indirectly in mitigating
neurodegenerative diseases, by preventing
protein self-association, slowing down the aggregation processes, and delaying the progression of AD.