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000840384 1001_ $$0P:(DE-Juel1)145867$$aDunkelmann, Tina$$b0
000840384 245__ $$aAβ oligomer eliminating compounds interfere successfully with pEAβ (3–42) induced motor neurodegenerative phenotype in transgenic mice
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000840384 520__ $$aCurrently, there are no causative or disease modifying treatments available for Alzheimer's disease (AD). Previously, it has been shown that D3, a small, fully d-enantiomeric peptide is able to eliminate low molecular weight Aβ oligomers in vitro, enhance cognition and reduce plaque load in AD transgenic mice. To further characterise the therapeutic potential of D3 towards N-terminally truncated and pyroglutamated Aβ (pEAβ(3–42)) we tested D3 and its head-to-tail tandem derivative D3D3 both in vitro and in vivo in the new mouse model TBA2.1. These mice produce human pEAβ(3–42) leading to a strong, early onset motor neurodegenerative phenotype. In the present study, we were able to demonstrate 1) strong binding affinity of both D3 and D3D3 to pEAβ(3–42) in comparison to Aβ(1–42) and 2) increased affinity of the tandem derivative D3D3 in comparison to D3. Subsequently we tested the therapeutic potentials of both peptides in the TBA2.1 animal model. Truly therapeutic, non-preventive treatment with D3 and D3D3 clearly slowed the progression of the neurodegenerative TBA2.1 phenotype, indicating the strong therapeutic potential of both peptides against pEAβ(3–42) induced neurodegeneration.
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000840384 7001_ $$0P:(DE-Juel1)164429$$aTeichmann, Kerstin$$b1
000840384 7001_ $$0P:(DE-Juel1)162487$$aZiehm, Tamar$$b2
000840384 7001_ $$0P:(DE-Juel1)165908$$aSchemmert, Sarah$$b3
000840384 7001_ $$0P:(DE-Juel1)145441$$aFrenzel, Daniel$$b4
000840384 7001_ $$0P:(DE-Juel1)131709$$aTusche, Markus$$b5
000840384 7001_ $$0P:(DE-Juel1)145961$$aDammers, Christina$$b6
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000840384 7001_ $$0P:(DE-Juel1)131777$$aLangen, Karl-Josef$$b8
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000840384 7001_ $$0P:(DE-Juel1)131794$$aShah, N. J.$$b10
000840384 7001_ $$0P:(DE-Juel1)159137$$aKutzsche, Janine$$b11
000840384 7001_ $$0P:(DE-Juel1)144347$$aWilluweit, Antje$$b12$$eCorresponding author
000840384 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b13$$eCorresponding author
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