title: Dense shell glycodendrimers as potential nontoxic anti-amyloidogenic agents in Alzheimer's disease. Amyloid-dendrimer aggregates morphology and cell toxicity.
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.
authors.affiliation: Biophysics Unit and Center of Studies in Biophysics, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Catalonia, Spain.
authors.forename: Oxana
authors.initials: O
authors.lastname: Klementieva
authors.forename: Núria
authors.initials: N
authors.lastname: Benseny-Cases
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gella
authors.forename: Dietmar
authors.initials: D
authors.lastname: Appelhans
authors.forename: Brigitte
authors.initials: B
authors.lastname: Voit
authors.forename: Josep
authors.initials: J
authors.lastname: Cladera
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000682:Amyloid / Q000737:chemistry / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008320:Maltose / Q000737:chemistry* / Q000494:pharmacology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry*; D011126:Polypropylenes / Q000737:chemistry* / Q000494:pharmacology; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D051381:Rats
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D050091:Dendrimers; D010446:Peptide Fragments; D011126:Polypropylenes; C078592:amyloid beta-protein (1-40); C443641:poly(propyleneimine); D008320:Maltose