Toward a Rational Design to Regulate β-Amyloid Fibrillation for Alzheimer's Disease Treatment

The last decades have witnessed a growing global burden of Alzheimer's disease (AD). Evidence indicates that the onset and progression of AD is associated with beta-amyloid (A beta) peptide fibrillation. As such, there is a strong passion with discovering potent A beta fibrillation inhibitors that can be developed into anti-amyloiddogenic agents for AD treatment. Current challenges that have arisen with this development involve with A beta oligomer toxicity suppression and Blood Brain Barrier penetration capability. Considering most natural or biological events, one would observe that there is usually a seed to direct natural materials to assemble in response to a certain stimulation. Inspired by this, several materials or compounds, including nanoparticle, peptide or peptide mimics, and organic molecules, have been designed for the purpose of redirecting or impeding A beta aggregation. Achieving these tasks requires comprehensive understanding on (1) initial A beta assembly into insoluble deposits, (2) main concerns with fibrillation inhibition, and (3) current major methodologies to disrupt the aggregation. Herein, the objective of this review is to address these three areas, and enable the pathway for a promising therapeutic agent design for AD treatment.