Impact of a discordant helix on β-amyloid structure, aggregation ability and toxicity

Abstract

According to amyloid cascade hypothesis, the deposit of amyloid-β (Aβ) peptide is the main cause of Alzheimer’s disease (AD). The aggregation ability and toxicity of Aβ peptides are highly associated with the sequence and conformation. A discordant helix is a helical segment with a tendency to form a β-strand conformation and has been found in many amyloid-like proteins or peptides. In this review, we summarize the current knowledge of the properties of a Aβ discordant helix and its impact on the Aβ structure, aggregation ability and cytotoxicity. In an Aβ sequence, a discordant helical region located at residue 15–26 has been proposed. This discordant helix plays a vital role in Aβ conformation, aggregation ability and cytotoxicity. Any factors which can stabilize the structure of the discordant helix may lead to the prevention of aggregation and toxicity of Aβ. This makes the discordant helix an attractive target for the design of new drugs for the treatment of AD.