Affiliations: [a] Department of Physics, Université de Montréal, Montreal, QC, Canada
| [b] Department of Chemistry, McGill University, Montreal, QC, Canada
| [c] INRS-Centre Armand-Frappier Santé Biotechnologie, Laval, QC, Canada
Correspondence:
[*]
Correspondence to: Charles Ramassamy, INRS-Centre Arm-and-Frappier Santé Biotechnologie, 531 boulevard des Prairies, Laval, Québec H7V 1B7, Canada. Tel.: + 1 450 687 5010; E-mail: Charles.Ramassamy@iaf.inrs.ca; Roger Gaudreault and Normand Mousseau, Department of Physics, Université de Montréal, Case postale 6128, succursale Centre-ville, Montreal, Québec, Canada. E-mail: Roger.Gaudreault@umontreal.ca, Normand.Mousseau@umontreal.ca.
Abstract: 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.
Keywords: Alzheimer’s disease, amyloid, blood cells, computer simulation, polyphenols, tau
