Dense shell glycodendrimers as potential nontoxic anti-amyloidogenic agents in Alzheimer's disease. Amyloid-dendrimer aggregates morphology and cell toxicity
(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.
(Less)
- author
- Klementieva, Oxana LU ; Benseny-Cases, Núria ; Gella, Alejandro ; Appelhans, Dietmar ; Voit, Brigitte and Cladera, Josep
- publishing date
- 2011-11-14
- 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 (ACS)
- external identifiers
-
- pmid:21936579
- 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
- 2024-08-06 02:27:43
@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}}, 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}}, language = {{eng}}, month = {{11}}, number = {{11}}, pages = {{9--3903}}, publisher = {{The American Chemical Society (ACS)}}, 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}}, doi = {{10.1021/bm2008636}}, volume = {{12}}, year = {{2011}}, }