Grant: Project Grant

Prion diseases (e.g. Creutzfeldt-Jakob disease) and Alzheimer's disease affect the brain, and to date there is no cure available for these deadly diseases. The cellular prion protein plays a critical role as a mediator of pathologies. Our goal is to interfere with the pathological function of the prion protein which enables us to develop treatments against both prion diseases and Alzheimer's disease. We have previously established peptide aptamers, small proteins which, similar to antibodies, were selected for binding to a particular target, that cover a specific part of the prion protein. This domain of the prion protein is a critical mediator of toxic effects of protein aggregates in Alzheimer's disease, and necessary for the formation of protein aggregates in prion diseases. Here, we will improve their strength of binding to the prion protein and their delivery to the brain, evaluate their therapeutic effects in mouse models of Alzheimer's disease and prion disease, and study cellular responses to the treatment. Overall, our studies will result in promising new treatment candidates for neurodegenerative diseases and unravel new knowledge about prion protein functions.