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@ARTICLE{Schartmann:848233,
author = {Schartmann, Elena and Schemmert, Sarah and Niemietz, Nicole
and Honold, Dominik and Ziehm, Tamar and Tusche, Markus and
Elfgen, Anne and Gering, Ian and Brener, Oleksandr and Shah,
Nadim Joni and Langen, Karl-Josef and Kutzsche, Janine and
Willbold, Dieter and Willuweit, Antje},
title = {{I}n {V}itro {P}otency and {P}reclinical {P}harmacokinetic
{C}omparison of {A}ll-{D}-{E}nantiomeric {P}eptides
{D}eveloped for the {T}reatment of {A}lzheimer’s
{D}isease},
journal = {Journal of Alzheimer's disease},
volume = {64},
number = {3},
issn = {1387-2877},
address = {Amsterdam},
publisher = {IOS Press},
reportid = {FZJ-2018-03495},
pages = {859 - 873},
year = {2018},
abstract = {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.},
cin = {ICS-6 / INM-4},
ddc = {610},
cid = {I:(DE-Juel1)ICS-6-20110106 / I:(DE-Juel1)INM-4-20090406},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29966196},
UT = {WOS:000437257500014},
doi = {10.3233/JAD-180165},
url = {https://juser.fz-juelich.de/record/848233},
}