Advances in Alzheimer's Disease-Associated A Therapy Based on Peptide

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 beta-amyloid (A beta) 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 A beta 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 A beta fibrosis or by computer aided drug design based on the structure of A beta. These peptide-based therapies can inhibit A beta fibrillation and reduce cytotoxicity induced by A beta aggregation and some have been shown to relieve cognition in AD model mice and reduce A beta plaques in mice brains. This review summarizes the design method and characteristics of peptide inhibitors and their effect on the amyloid fibrosis of A beta. 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.