title: Dendrimers reduce toxicity of Aβ 1-28 peptide during aggregation and accelerate fibril formation.
abstract: The influence of a GATG (gallic acid-triethylene glycol) dendrimer decorated with 27 terminal morpholine groups ([G3]-Mor) on the aggregation process of Alzheimer's peptide has been investigated. Amyloid fibrils were formed from the Aβ 1-28 peptide and the process was monitored by a ThT assay, changes in CD spectra, and transmission electron microscopy. In the presence of [G3]-Mor, more fibrils were built and the process significantly accelerated compared with a control. The cytotoxicity of (1) Aβ and (2) the system [G3]-Mor/Aβ was monitored at different stages of the aggregation process. Prefibrillar species were more toxic than mature fibrils. [G3]-Mor significantly reduced the toxicity of Aβ, probably because of lowering the amount of prefibrillar forms in the system by speeding up the process of fibril formation.
  
  
  BACKGROUND
  In this study, GATG dendrimer decorated with 27 terminal morpholine groups was able to reduce beta-amyloid fibril formation, which might represent a new method to address the key pathology in Alzheimer's disease.
authors.affiliation: Department of General Biophysics, University of Lodz, Lodz, Poland. aklajn@biol.uni.lodz.pl
authors.forename: Barbara
authors.initials: B
authors.lastname: Klajnert
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wasiak
authors.forename: Maksim
authors.initials: M
authors.lastname: Ionov
authors.forename: Marcos
authors.initials: M
authors.lastname: Fernandez-Villamarin
authors.forename: Ana
authors.initials: A
authors.lastname: Sousa-Herves
authors.forename: Juan
authors.initials: J
authors.lastname: Correa
authors.forename: Ricardo
authors.initials: R
authors.lastname: Riguera
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandez-Megia
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D050091:Dendrimers / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005707:Gallic Acid / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D050091:Dendrimers; D010446:Peptide Fragments; C084358:amyloid beta-protein (1-28); C028914:triethylene glycol; D011092:Polyethylene Glycols; D005707:Gallic Acid