Dense shell glycodendrimers as potential nontoxic anti-amyloidogenic agents in Alzheimer's disease. Amyloid-dendrimer aggregates morphology and cell toxicity

Research output: Contribution to journalArticle

Abstract

Dendrimers have been proved to interact with amyloids, although most of dendrimers assayed in amyloidogenic systems are toxic to cells. The development of glycodendrimers, poly(propyleneimine) (PPI) dendrimers decorated with maltose (Mal), represents the possibility of using dendrimers with a low intrinsic toxicity. In the present paper we show that fourth (PPI-G4-Mal) and fifth (PPI-G5-Mal) generation glycodendrimers have the capacity to interfere with Alzheimer's amyloid peptide Aβ(1-40) fibrilization. The interaction is generation dependent: PPI-G5-Mal blocks amyloid fibril formation generating granular nonfibrillar amorphous aggregates, whereas PPI-G4-Mal generates clumped fibrils at low dendrimer-peptide ratios and amorphous aggregates at high ratios. Both PPI-G4-Mal and PPI-G5-Mal are nontoxic to PC12 and SH-SY5Y cells. PPI-G4-Mal reduces amyloid toxicity by clumping fibrils together, whereas amorphous aggregates are toxic to PC12 cells. The results show that glycodendrimers are promising nontoxic agents in the search for anti-amyloidogenic compounds. Fibril clumping may be an anti-amyloid toxicity strategy.

Details

Authors
  • Oxana Klementieva
  • Núria Benseny-Cases
  • Alejandro Gella
  • Dietmar Appelhans
  • Brigitte Voit
  • Josep Cladera
External organisations
  • Autonomous University of Barcelona
Research areas and keywords

Keywords

  • Alzheimer Disease/drug therapy, Amyloid/chemistry, Amyloid beta-Peptides/chemistry, Animals, Cell Line, Tumor, Cell Survival, Dendrimers/chemistry, Humans, Kinetics, Maltose/chemistry, PC12 Cells, Peptide Fragments/chemistry, Polypropylenes/chemistry, Protein Multimerization, Protein Structure, Quaternary, Rats
Original languageEnglish
Pages (from-to)3903-9
JournalBiomacromolecules
Volume12
Issue number11
Publication statusPublished - 2011 Nov 14
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes