A beta oligomer eliminating compounds interfere successfully with pEA beta(3-42) induced motor neurodegenerative phenotype in transgenic mice

作者：Dunkelmann Tina; Teichmann Kerstin; Ziehm Tamar; Schemmert Sarah; Frenzel Daniel; Tusche Markus; Dammers Christina; Juergens Dagmar; Langen Karl Josef; Demuth Hans Ulrich; Shah Nadim Jon; Kutzsche Janine; Willuweit Antje^*; Willbold Dieter^*

来源：Neuropeptides, 2018, 67: 27-35.

DOI：10.1016/j.npep.2017.11.011

• pEA beta(3-42)
• D3
• D3D3
• Neurodegeneration
• Alzheimer's disease
• Animal model
• Treatment
• All-D-enantiomeric peptides
• TBA2.1

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 A beta 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 All (pEA beta(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 pEA beta(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 pEA beta(3-42) in comparison to A beta(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 pEA beta(3-42) induced neurodegeneration.

• 出版日期2018-2