Targeting PrPC-Aβ oligomer-interaction using peptide aptamers: a novel approach for treatment of Alzheimer’s disease

• Applicant: Dr. Antonia Nicole Klein
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 383698497

Alzheimer’s disease is a disease of the central nervous system, accounting for 60 – 80 % of dementia cases. There is no causal therapy for this progressive disease available. Accumulation of soluble Amyloid-beta peptides, so called Abeta oligomers, are thought to be responsible for neuronal death, leads to lack of transfer of brain activity, and ultimately to cognitive impairments. The interaction between Abeta oligomers and cellular prion protein (PrPC) is one possible mechanism which explains these pathological events. In this study a new therapeutic drug against Alzheimer’s disease will be developed by inhibition of the PrPC-Abeta Oligomer interaction using peptide aptamers (PA). PA each consist of 16-20 amino acids integrated within a scaffold protein. This scaffold protein stabilizes the structure and increases the binding affinity to the target compared to the native peptide. Two different sets of PA will be used to inhibit the PrPC-Abeta Oligomere interaction: PAs, which bind to PrPC at the binding epitope of the PrPC-Abeta oligomer interaction; and PrP-PAs, which are PrPC-adapted and bind to Abeta oligomers. The influence of this PA on the PrPC-Abeta oligomer interaction and the resulting reduced pathological effect of Abeta oligomers on neuronal cells will be analyzed in cell culture and mice models.

• DFG Programme: Research Fellowships
• International Connection: Canada
• Host: Dr. Sabine Gilch