TY  - JOUR
AU  - Schemmert, Sarah
AU  - Schartmann, Elena
AU  - Honold, Dominik
AU  - Zafiu, Christian
AU  - Ziehm, Tamar
AU  - Langen, Karl-Josef
AU  - Shah, Nadim Joni
AU  - Kutzsche, Janine
AU  - Willuweit, Antje
AU  - Willbold, Dieter
TI  - Deceleration of the neurodegenerative phenotype in pyroglutamate-Aβ accumulating transgenic mice by oral treatment with the Aβ oligomer eliminating compound RD2
JO  - Neurobiology of disease
VL  - 124
SN  - 0969-9961
CY  - Orlando, Fla.
PB  - Academic Press
M1  - FZJ-2018-06329
SP  - 36-45
PY  - 2019
AB  - Alzheimer'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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30391539
UR  - <Go to ISI:>//WOS:000459217800004
DO  - DOI:10.1016/j.nbd.2018.10.021
UR  - https://juser.fz-juelich.de/record/857061
ER  -