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000809114 1001_ $$0P:(DE-Juel1)145785$$aKlein, Antonia Nicole$$b0
000809114 245__ $$aOptimization of the All-D Peptide D3 for Aβ Oligomer Elimination
000809114 260__ $$aLawrence, Kan.$$bPLoS$$c2016
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000809114 520__ $$aThe aggregation of amyloid-β (Aβ) is postulated to be the crucial event in Alzheimer’s disease (AD). In particular, small neurotoxic Aβ oligomers are considered to be responsible for the development and progression of AD. Therefore, elimination of thesis oligomers represents a potential causal therapy of AD. Starting from the well-characterized D-enantiomeric peptide D3, we identified D3 derivatives that bind monomeric Aβ. The underlying hypothesis is that ligands bind monomeric Aβ and stabilize these species within the various equilibria with Aβ assemblies, leading ultimately to the elimination of Aβ oligomers. One of the hereby identified D-peptides, DB3, and a head-to-tail tandem of DB3, DB3DB3, were studied in detail. Both peptides were found to: (i) inhibit the formation of Thioflavin T-positive fibrils; (ii) bind to Aβ monomers with micromolar affinities; (iii) eliminate Aβ oligomers; (iv) reduce Aβ-induced cytotoxicity; and (v) disassemble preformed Aβ aggregates. The beneficial effects of DB3 were improved by DB3DB3, which showed highly enhanced efficacy. Our approach yielded Aβ monomer-stabilizing ligands that can be investigated as a suitable therapeutic strategy against AD.
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000809114 7001_ $$0P:(DE-Juel1)162487$$aZiehm, Tamar$$b1$$ufzj
000809114 7001_ $$0P:(DE-Juel1)131709$$aTusche, Markus$$b2$$ufzj
000809114 7001_ $$0P:(DE-Juel1)130577$$aBuitenhuis, Johan$$b3$$ufzj
000809114 7001_ $$0P:(DE-Juel1)131991$$aBartnik, Dirk$$b4
000809114 7001_ $$0P:(DE-HGF)0$$aBoeddrich, Annett$$b5
000809114 7001_ $$0P:(DE-HGF)0$$aWiglenda, Thomas$$b6
000809114 7001_ $$0P:(DE-HGF)0$$aWanker, Erich$$b7
000809114 7001_ $$0P:(DE-HGF)0$$aFunke, Susanne Aileen$$b8
000809114 7001_ $$0P:(DE-HGF)0$$aBrener, Oleksandr$$b9
000809114 7001_ $$0P:(DE-Juel1)145165$$aGremer, Lothar$$b10$$ufzj
000809114 7001_ $$0P:(DE-Juel1)159137$$aKutzsche, Janine$$b11$$ufzj
000809114 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b12$$eCorresponding author$$ufzj
000809114 773__ $$0PERI:(DE-600)2267670-3$$a10.1371/journal.pone.0153035$$gVol. 11, no. 4, p. e0153035 -$$n4$$pe0153035 -$$tPLoS one$$v11$$x1932-6203$$y2016
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