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000857061 1001_ $$0P:(DE-Juel1)165908$$aSchemmert, Sarah$$b0$$ufzj
000857061 245__ $$aDeceleration of the neurodegenerative phenotype in pyroglutamate-Aβ accumulating transgenic mice by oral treatment with the Aβ oligomer eliminating compound RD2
000857061 260__ $$aOrlando, Fla.$$bAcademic Press$$c2019
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000857061 520__ $$aAlzheimer's disease, a multifactorial incurable disorder, is mainly characterised by progressive neurodegeneration, extracellular accumulation of amyloid-β protein (Aβ), and intracellular aggregation of hyperphosphorylated tau protein. During the last years, Aβ oligomers have been claimed to be the disease causing agent. Consequently, development of compounds that are able to disrupt already existing Aβ oligomers is highly desirable. We developed d-enantiomeric peptides, consisting solely of d-enantiomeric amino acid residues, for the direct and specific elimination of toxic Aβ oligomers. The drug candidate RD2 did show high oligomer elimination efficacy in vitro and the in vivo efficacy of RD2 was demonstrated in treatment studies by enhanced cognition in transgenic mouse models of amyloidosis. Here, we report on the in vitro and in vivo efficacy of the compound towards pyroglutamate-Aβ, a particular aggressive Aβ species. Using the transgenic TBA2.1 mouse model, which develops pyroglutamate-Aβ(3–42) induced neurodegeneration, we are able to show that oral RD2 treatment resulted in a significant deceleration of the progression of the phenotype. The in vivo efficacy against this highly toxic Aβ species further validates RD2 as a drug candidate for the therapeutic use in humans.
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000857061 7001_ $$0P:(DE-Juel1)166069$$aSchartmann, Elena$$b1
000857061 7001_ $$0P:(DE-Juel1)164541$$aHonold, Dominik$$b2$$ufzj
000857061 7001_ $$0P:(DE-Juel1)162137$$aZafiu, Christian$$b3$$ufzj
000857061 7001_ $$0P:(DE-Juel1)162487$$aZiehm, Tamar$$b4$$ufzj
000857061 7001_ $$0P:(DE-Juel1)131777$$aLangen, Karl-Josef$$b5$$ufzj
000857061 7001_ $$0P:(DE-Juel1)131794$$aShah, Nadim Joni$$b6$$ufzj
000857061 7001_ $$0P:(DE-Juel1)159137$$aKutzsche, Janine$$b7$$ufzj
000857061 7001_ $$0P:(DE-Juel1)144347$$aWilluweit, Antje$$b8$$eCorresponding author$$ufzj
000857061 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b9$$eCorresponding author
000857061 773__ $$0PERI:(DE-600)1471408-5$$a10.1016/j.nbd.2018.10.021$$gp. S0969996118307320$$p36-45$$tNeurobiology of disease$$v124$$x0969-9961$$y2019
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