Phosphorus-containing dendrimers against α-synuclein fibril formation

Int J Biol Macromol. 2012 May 1;50(4):1138-43. doi: 10.1016/j.ijbiomac.2012.02.003. Epub 2012 Feb 13.

Abstract

The aim of this work was to study the effect of phosphorus-containing dendrimers (generations G3 and G4) on the fibrillation of α-synuclein (ASN). The inhibition of fibril formation (filamentous and aggregates) is a potential therapeutic strategy for neurodegenerative disorders such as Parkinson's and other motor disorder neurodegenerative diseases. The interaction between phosphorus-containing dendrimers and ASN was studied by fluorescence spectroscopy. The decrease in the fluorescence intensity of intrisinic tyrosine was the most marked change in the fluorescence intensity observed upon addition of dendrimers. Furthermore, the effect of dendrimers on ASN fibril formation was studied using circular dichroism (CD) spectroscopy and CD studies were complemented by fluorescence assays using the dye thioflavin T (ThT). The results showed that phosphorus-containing dendrimers G3 and G4 inhibited fibril formation, when they were used in the ASN/dendrimer ratios 1:0.1 and 1:0.5. However, the higher concentrations of dendrimers did not show this effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / pharmacology*
  • Dendrimers / chemistry*
  • Dendrimers / pharmacology*
  • Humans
  • Phosphates / chemistry
  • Phosphorus / chemistry*
  • Protein Multimerization / drug effects*
  • Protein Structure, Secondary / drug effects
  • alpha-Synuclein / chemistry*

Substances

  • Biocompatible Materials
  • Dendrimers
  • Phosphates
  • alpha-Synuclein
  • Phosphorus
  • thiophosphoric acid