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@ARTICLE{Dunkelmann:840384,
author = {Dunkelmann, Tina and Teichmann, Kerstin and Ziehm, Tamar
and Schemmert, Sarah and Frenzel, Daniel and Tusche, Markus
and Dammers, Christina and Jürgens, Dagmar and Langen,
Karl-Josef and Demuth, Hans-Ulrich and Shah, N. J. and
Kutzsche, Janine and Willuweit, Antje and Willbold, Dieter},
title = {{A}β oligomer eliminating compounds interfere successfully
with p{EA}β (3–42) induced motor neurodegenerative
phenotype in transgenic mice},
journal = {Neuropeptides},
volume = {67},
issn = {0143-4179},
address = {[New York, NY]},
publisher = {Elsevier},
reportid = {FZJ-2017-07917},
pages = {27-35},
year = {2018},
abstract = {Currently, there are no causative or disease modifying
treatments available for Alzheimer's disease (AD).
Previously, it has been shown that D3, a small, fully
d-enantiomeric peptide is able to eliminate low molecular
weight Aβ oligomers in vitro, enhance cognition and reduce
plaque load in AD transgenic mice. To further characterise
the therapeutic potential of D3 towards N-terminally
truncated and pyroglutamated Aβ (pEAβ(3–42)) we tested
D3 and its head-to-tail tandem derivative D3D3 both in vitro
and in vivo in the new mouse model TBA2.1. These mice
produce human pEAβ(3–42) leading to a strong, early onset
motor neurodegenerative phenotype. In the present study, we
were able to demonstrate 1) strong binding affinity of both
D3 and D3D3 to pEAβ(3–42) in comparison to Aβ(1–42)
and 2) increased affinity of the tandem derivative D3D3 in
comparison to D3. Subsequently we tested the therapeutic
potentials of both peptides in the TBA2.1 animal model.
Truly therapeutic, non-preventive treatment with D3 and D3D3
clearly slowed the progression of the neurodegenerative
TBA2.1 phenotype, indicating the strong therapeutic
potential of both peptides against pEAβ(3–42) induced
neurodegeneration.},
cin = {ICS-6 / INM-4 / JARA-BRAIN},
ddc = {610},
cid = {I:(DE-Juel1)ICS-6-20110106 / I:(DE-Juel1)INM-4-20090406 /
$I:(DE-82)080010_20140620$},
pnm = {573 - Neuroimaging (POF3-573)},
pid = {G:(DE-HGF)POF3-573},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29273382},
UT = {WOS:000425556500004},
doi = {10.1016/j.npep.2017.11.011},
url = {https://juser.fz-juelich.de/record/840384},
}