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000848233 1001_ $$0P:(DE-Juel1)166069$$aSchartmann, Elena$$b0$$ufzj
000848233 245__ $$aIn Vitro Potency and Preclinical Pharmacokinetic Comparison of All-D-Enantiomeric Peptides Developed for the Treatment of Alzheimer’s Disease
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000848233 520__ $$aDiffusible 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.
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000848233 7001_ $$0P:(DE-Juel1)165908$$aSchemmert, Sarah$$b1$$ufzj
000848233 7001_ $$0P:(DE-Juel1)173023$$aNiemietz, Nicole$$b2$$ufzj
000848233 7001_ $$0P:(DE-Juel1)164541$$aHonold, Dominik$$b3$$ufzj
000848233 7001_ $$0P:(DE-Juel1)162487$$aZiehm, Tamar$$b4$$ufzj
000848233 7001_ $$0P:(DE-Juel1)131709$$aTusche, Markus$$b5$$ufzj
000848233 7001_ $$0P:(DE-Juel1)164354$$aElfgen, Anne$$b6$$ufzj
000848233 7001_ $$0P:(DE-Juel1)171922$$aGering, Ian$$b7$$ufzj
000848233 7001_ $$0P:(DE-HGF)0$$aBrener, Oleksandr$$b8
000848233 7001_ $$0P:(DE-Juel1)131794$$aShah, Nadim Joni$$b9$$ufzj
000848233 7001_ $$0P:(DE-Juel1)131777$$aLangen, Karl-Josef$$b10$$ufzj
000848233 7001_ $$0P:(DE-Juel1)159137$$aKutzsche, Janine$$b11$$ufzj
000848233 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b12$$eCorresponding author$$ufzj
000848233 7001_ $$0P:(DE-Juel1)144347$$aWilluweit, Antje$$b13$$eCorresponding author$$ufzj
000848233 773__ $$0PERI:(DE-600)2070772-1$$a10.3233/JAD-180165$$gVol. 64, no. 3, p. 859 - 873$$n3$$p859 - 873$$tJournal of Alzheimer's disease$$v64$$x1387-2877$$y2018
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