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

Klementieva, Oxana LU ; Benseny-Cases, Núria; Gella, Alejandro; Appelhans, Dietmar; Voit, Brigitte and Cladera, Josep (2011) In Biomacromolecules 12(11). p.9-3903
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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
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
in
Biomacromolecules
volume
12
issue
11
pages
9 - 3903
publisher
The American Chemical Society
external identifiers
  • scopus:81255152309
ISSN
1526-4602
DOI
10.1021/bm2008636
language
English
LU publication?
no
id
264ccfaf-861b-4ff8-8246-b5ca9bb82ac5
date added to LUP
2018-11-01 13:26:40
date last changed
2019-08-14 04:26:27
@article{264ccfaf-861b-4ff8-8246-b5ca9bb82ac5,
  abstract     = {<p>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.</p>},
  author       = {Klementieva, Oxana and Benseny-Cases, Núria and Gella, Alejandro and Appelhans, Dietmar and Voit, Brigitte and Cladera, Josep},
  issn         = {1526-4602},
  keyword      = {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},
  language     = {eng},
  month        = {11},
  number       = {11},
  pages        = {9--3903},
  publisher    = {The American Chemical Society},
  series       = {Biomacromolecules},
  title        = {Dense shell glycodendrimers as potential nontoxic anti-amyloidogenic agents in Alzheimer's disease. Amyloid-dendrimer aggregates morphology and cell toxicity},
  url          = {http://dx.doi.org/10.1021/bm2008636},
  volume       = {12},
  year         = {2011},
}