A specific inhibitory effect of multivalent trehalose toward Aβ(1-40) aggregation

Abstract

The inhibitory effect of disaccharides and their polyvalent compounds toward aggregation of Aβ(1-40) was investigated. Polyvalent trehalose, maltose and lactose were synthesized, and their inhibitory effects were investigated together with those of the corresponding monomeric disaccharides. The inhibitory effects of the monomeric disaccharides were weak, but were amplified by multivalency. Trehalose and polyvalent trehalose induced formation of aggregates with specific pseudo-spherical morphology, which did not occur in the presence of the other disaccharides or in the absence of additives. Addition of polyvalent trehalose neutralized the cytotoxicity of Aβ, while monomeric trehalose induced weak cytotoxicity (toward HeLa cells). The specific inhibitory effects of trehalose and polyvalent trehalose on Aβ aggregation are discussed in the terms of the conformation of those molecules.