Breaker peptides against amyloid-β aggregation: a potential therapeutic strategy for Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, for whichblocking the early steps of extracellular misfolded amyloid-β (Aβ) aggregation is a promising therapeutic approach. However, the pathological features of AD progression includethe accumulation of intracellular tau protein, membrane-catalyzed cell deathand the abnormal deposition of Aβ. Here, we focus on anti-amyloid breaker peptides derived from the Aβ sequence and non-Aβ-based peptidescontaining both natural and modified amino acids. Critical aspects of the breaker peptides include N-methylation, conformational restriction through cyclization, incorporation of unnatural amino acid, fluorinated molecules, polymeric nanoparticles andPEGylation. This review confers a general idea of such breaker peptides with in vitro and in vivo studies, which may advance our understanding of AD pathology and develop an effective treatment strategy against AD.