TY  - JOUR
AU  - Klein, Antonia Nicole
AU  - Ziehm, Tamar
AU  - Tusche, Markus
AU  - Buitenhuis, Johan
AU  - Bartnik, Dirk
AU  - Boeddrich, Annett
AU  - Wiglenda, Thomas
AU  - Wanker, Erich
AU  - Funke, Susanne Aileen
AU  - Brener, Oleksandr
AU  - Gremer, Lothar
AU  - Kutzsche, Janine
AU  - Willbold, Dieter
TI  - Optimization of the All-D Peptide D3 for Aβ Oligomer Elimination
JO  - PLoS one
VL  - 11
IS  - 4
SN  - 1932-6203
CY  - Lawrence, Kan.
PB  - PLoS
M1  - FZJ-2016-02505
SP  - e0153035 -
PY  - 2016
AB  - The aggregation of amyloid-β (Aβ) is postulated to be the crucial event in Alzheimer’s disease (AD). In particular, small neurotoxic Aβ oligomers are considered to be responsible for the development and progression of AD. Therefore, elimination of thesis oligomers represents a potential causal therapy of AD. Starting from the well-characterized D-enantiomeric peptide D3, we identified D3 derivatives that bind monomeric Aβ. The underlying hypothesis is that ligands bind monomeric Aβ and stabilize these species within the various equilibria with Aβ assemblies, leading ultimately to the elimination of Aβ oligomers. One of the hereby identified D-peptides, DB3, and a head-to-tail tandem of DB3, DB3DB3, were studied in detail. Both peptides were found to: (i) inhibit the formation of Thioflavin T-positive fibrils; (ii) bind to Aβ monomers with micromolar affinities; (iii) eliminate Aβ oligomers; (iv) reduce Aβ-induced cytotoxicity; and (v) disassemble preformed Aβ aggregates. The beneficial effects of DB3 were improved by DB3DB3, which showed highly enhanced efficacy. Our approach yielded Aβ monomer-stabilizing ligands that can be investigated as a suitable therapeutic strategy against AD.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000374565100009
DO  - DOI:10.1371/journal.pone.0153035
UR  - https://juser.fz-juelich.de/record/809114
ER  -