PAMAM dendrimers as potential agents against fibrillation of alpha-synuclein, a Parkinson's disease-related protein

Abstract

The effect of PAMAM dendrimers (generations G3, G4 and G5) on the fibrillation of alpha-synuclein was examined by fluorescence and CD spectroscopy, TEM and SANS. PAMAM dendrimers inhibited fibrillation of alpha-synuclein and this effect increased both with generation number and PAMAM concentration. SANS showed structural changes in the formed aggregates of alpha-synuclein--from cylindrical to dense three-dimensional ones--as the PAMAM concentration increased, on account of the inhibitory effect. PAMAM also effectively promoted the breaking down of pre-existing fibrils of alpha-synuclein. In both processes--that is, inhibition and disassociation of fibrils--PAMAM redirected alpha-synuclein to an amorphous aggregation pathway.