Influence of in vitro neuronal membranes on the anti-amyloidogenic activity of gallic acid: Implication for the therapy of Alzheimer's disease

Abstract

Molecules inhibiting the amyloid beta (Aβ) peptide aggregation and/or disaggregating mature fibrils are a promising approach for the Alzheimer's disease (AD) therapy, as the Aβ fibrillation is one of the key triggers of the disease. Gallic acid (GA) is a phenolic acid with anti-amyloidogenic activity against Aβ in buffered solutions. However, there is still no evidence of these properties in vivo. Given the rate of failures of AD drug development, there is a huge demand of replicating the in vivo environment in in vitro studies, thus allowing to stop earlier the study of molecules with no effect in vivo. Thus, this study aims to evaluate the effect of in vitro neuronal membranes on the GA's ability in preventing Aβ1-42 aggregation and disrupting preformed fibrils. To this end, liposomes were employed to mimic the cell membrane environment. The results reveal that the lipid membranes did not affect the GA's ability in inhibiting Aβ1−42 fibrillation. However, in vitro neuronal membranes modulate the GA-induced Aβ fibrils disaggregation, which may be related with the moderate affinity of the compound for the lipid membrane. Even so, GA presented strong anti-amyloidogenic properties in the cell membrane-like environment. This work highlights the promising value of GA on preventing and treating AD, thus justifying its study in animal models.