Mitigating Alzheimer's Disease with Natural Polyphenols: A Review

According to Alzheimer's Disease International (ADI), nearly 50 million people worldwide were living with dementia in 2017, and this number is expected to triple by 2050. Despite years of research in this field, the root cause and mechanisms responsible for Alzheimer's disease (AD) have not been fully elucidated yet. Moreover, promising preclinical results have repeatedly failed to translate into patient treatments. Until now, none of the molecules targeting AD has successfully passed the Phase III trial. Although natural molecules have been extensively studied, they normally require high concentrations to be effective; alternately, they are too large to cross the blood-brain barrier (BBB). In this review, we report AD treatment strategies, with a virtually exclusive focus on green chemistry (natural phenolic molecules). These include therapeutic strategies for decreasing amyloid-β (Aβ) production, preventing and/or altering Aβ aggregation, and reducing oligomers cytotoxicity such as curcumin, (-)-epigallocatechin-3-gallate (EGCG), morin, resveratrol, tannic acid, and other natural green molecules. We also examine whether consideration should be given to potential candidates used outside of medicine and nutrition, through a discussion of two intermediate-sized green molecules, with very similar molecular structures and key properties, which exhibit potential in mitigating Alzheimer's disease.