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| 100 | 1 | _ | |a Schartmann, Elena |0 P:(DE-Juel1)166069 |b 0 |u fzj |
| 245 | _ | _ | |a In Vitro Potency and Preclinical Pharmacokinetic Comparison of All-D-Enantiomeric Peptides Developed for the Treatment of Alzheimer’s Disease |
| 260 | _ | _ | |a Amsterdam |c 2018 |b IOS Press |
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| 520 | _ | _ | |a 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. |
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| 700 | 1 | _ | |a Honold, Dominik |0 P:(DE-Juel1)164541 |b 3 |u fzj |
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| 773 | _ | _ | |a 10.3233/JAD-180165 |g Vol. 64, no. 3, p. 859 - 873 |0 PERI:(DE-600)2070772-1 |n 3 |p 859 - 873 |t Journal of Alzheimer's disease |v 64 |y 2018 |x 1387-2877 |
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