Advances in Alzheimer’s Disease-Associated Aβ Therapy Based on Peptide

Abstract

Alzheimer’s disease (AD) urgently needs innovative treatments due to the increasing aging population and lack of effective drugs and therapies. The amyloid fibrosis of AD-associated β-amyloid (Aβ) that could induce a series of cascades, such as oxidative stress and inflammation, is a critical factor in the progression of AD. Recently, peptide-based therapies for AD are expected to be great potential strategies for the high specificity to the targets, low toxicity, fast blood clearance, rapid cell and tissue permeability, and superior biochemical characteristics. Specifically, various chiral amino acids or peptide-modified interfaces draw much attention as effective manners to inhibit Aβ fibrillation. On the other hand, peptide-based inhibitors could be obtained through affinity screening such as phage display or by rational design based on the core sequence of Aβ fibrosis or by computer aided drug design based on the structure of Aβ. These peptide-based therapies can inhibit Aβ fibrillation and reduce cytotoxicity induced by Aβ aggregation and some have been shown to relieve cognition in AD model mice and reduce Aβ plaques in mice brains. This review summarizes the design method and characteristics of peptide inhibitors and their effect on the amyloid fibrosis of Aβ. We further describe some analysis methods for evaluating the inhibitory effect and point out the challenges in these areas, and possible directions for the design of AD drugs based on peptides, which lay the foundation for the development of new effective drugs in the future.