SMALL INTERFERENCE PEPTIDES AS BLOCKERS OF BETA-AMYLOID AGGREGATION

Abstract

In Alzheimer's disease (AD) pathogenesis, the conversion of the beta-amyloid (Aβ) peptide from its soluble monomeric form into various aggregated some has been recognized as one of the key step. Aβ peptides form toxic assemblies ranging in size from small oligomers (2–8 amino acids) to large fibrils. Several studies have shown that Aβ soluble oligomers play a major role in disease pathogenesis. Although it's still unclear how these amyloidogenic protein misfold and form toxic assemblies, inhibiting Aβ self-oligomerization could provide an approach to treating the underlying cause of AD. Here, we designed potential peptide-based aggregation inhibitors, using an overlapping peptides array technology, to effectively interfere with Aβ self-association. Using High Performance Liquid Chromatography (HPLC) to analyze the composition of Aβ oligomers. ThT and ANS assays, by detecting the β-sheet conformation and hydrophobic structure in the protein, also confirmed the effectiveness of the small interference peptides inhibiting Aβ self-association. We found that our small interference peptides could effectively block the small oligomers formation. ThT and ANS assays, by detecting the β-sheet conformation and hydrophobic structure in the protein, also confirmed the effectiveness of the small interference peptides inhibiting Aβ self-association. Our small interference peptides, which consist of short complimentary segments of the beta-amyloid protein, can be useful for identifying the aggregation-prone regions of the amyloid protein for drug discovery and development of potential therapeutic reagents.