PAMAM dendrimers as potential agents against fibrillation of alpha-synuclein, a Parkinson's disease-related protein.
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.
Rekas
Agata
A
Australian Nuclear Science and Technology Organization, PMB 1, Menai, NSW 2234, Australia.
Lo
Victor
V
Gadd
Gerry E
GE
Cappai
Roberto
R
Yun
Seok I
SI
D050091:Dendrimers; D006801:Humans; D010300:Parkinson Disease / Q000517:prevention & control; D011073:Polyamines / Q000494:pharmacology* / Q000627:therapeutic use; D011108:Polymers; D011487:Protein Conformation / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D013057:Spectrum Analysis; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D011108:Polymers; D051844:alpha-Synuclein