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

Macromol Biosci. 2009 Mar 10;9(3):230-8. doi: 10.1002/mabi.200800242.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Dendrimers
  • Humans
  • Parkinson Disease / prevention & control
  • Polyamines / pharmacology*
  • Polyamines / therapeutic use
  • Polymers
  • Protein Conformation / drug effects
  • Protein Multimerization / drug effects
  • Spectrum Analysis
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / metabolism*

Substances

  • Dendrimers
  • PAMAM Starburst
  • Polyamines
  • Polymers
  • alpha-Synuclein