%0 Journal Article
%A Schartmann, Elena
%A Schemmert, Sarah
%A Niemietz, Nicole
%A Honold, Dominik
%A Ziehm, Tamar
%A Tusche, Markus
%A Elfgen, Anne
%A Gering, Ian
%A Brener, Oleksandr
%A Shah, Nadim Joni
%A Langen, Karl-Josef
%A Kutzsche, Janine
%A Willbold, Dieter
%A Willuweit, Antje
%T In Vitro Potency and Preclinical Pharmacokinetic Comparison of All-D-Enantiomeric Peptides Developed for the Treatment of Alzheimer’s Disease
%J Journal of Alzheimer's disease
%V 64
%N 3
%@ 1387-2877
%C Amsterdam
%I IOS Press
%M FZJ-2018-03495
%P 859 - 873
%D 2018
%X Diffusible amyloid-β (Aβ) oligomers are currently presumed to be the most cytotoxic Aβ assembly and held responsible to trigger the pathogenesis of Alzheimer’s disease (AD). Thus, Aβ oligomers are a prominent target in AD drug development. Previously, we reported on our solely D-enantiomeric peptide D3 and its derivatives as AD drug candidates. Here, we compare one of the most promising D3 derivatives, ANK6, with its tandem version (tANK6), and its head-to-tail cyclized isoform (cANK6r). In vitro tests investigating the D-peptides’ potencies to inhibit Aβ aggregation, eliminate Aβ oligomers, and reduce Aβ-induced cytotoxicity revealed that all three D-peptides efficiently target Aβ. Subsequent preclinical pharmacokinetic studies of the three all-D-peptides in wildtype mice showed promising blood-brain barrier permeability with cANK6r yielding the highest levels in brain. The peptides’ potencies to lower Aβ toxicity and their remarkable brain/plasma ratios make them promising AD drug candidates.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:29966196
%U <Go to ISI:>//WOS:000437257500014
%R 10.3233/JAD-180165
%U https://juser.fz-juelich.de/record/848233