TY  - JOUR
AU  - Schartmann, Elena
AU  - Schemmert, Sarah
AU  - Niemietz, Nicole
AU  - Honold, Dominik
AU  - Ziehm, Tamar
AU  - Tusche, Markus
AU  - Elfgen, Anne
AU  - Gering, Ian
AU  - Brener, Oleksandr
AU  - Shah, Nadim Joni
AU  - Langen, Karl-Josef
AU  - Kutzsche, Janine
AU  - Willbold, Dieter
AU  - Willuweit, Antje
TI  - In Vitro Potency and Preclinical Pharmacokinetic Comparison of All-D-Enantiomeric Peptides Developed for the Treatment of Alzheimer’s Disease
JO  - Journal of Alzheimer's disease
VL  - 64
IS  - 3
SN  - 1387-2877
CY  - Amsterdam
PB  - IOS Press
M1  - FZJ-2018-03495
SP  - 859 - 873
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29966196
UR  - <Go to ISI:>//WOS:000437257500014
DO  - DOI:10.3233/JAD-180165
UR  - https://juser.fz-juelich.de/record/848233
ER  -