Dendrimers reduce toxicity of Aβ 1-28 peptide during aggregation and accelerate fibril formation

The influence of a GATG (gallic acid-triethylene glycol) dendrimer decorated with 27 terminal morpholine groups ([G3]-Mor) on the aggregation process of Alzheimer's peptide has been investigated. Amyloid fibrils were formed from the A beta 1-28 peptide and the process was monitored by a ThT assay, changes in CD spectra, and transmission electron microscopy. In the presence of [G3]-Mor, more fibrils were built and the process significantly accelerated compared with a control. The cytotoxicity of (1) A beta and (2) the system [G3]-Mor/A beta was monitored at different stages of the aggregation process. Prefibrillar species were more toxic than mature fibrils. [G3]-Mor significantly reduced the toxicity of A beta, probably because of lowering the amount of prefibrillar forms in the system by speeding up the process of fibril formation.