A relevant fraction of the cellular prion protein (PrP^C) on our neurons is constantly cut into smaller pieces by molecular scissors termed “proteases”. These cleavages reduce amounts of the prion protein as a substrate for the detrimental three-dimensional misfolding underlying fatal prion diseases. In addition, cleaved parts of the prion protein are released from the neuronal surface as soluble fragments. The latter may act as protective factors by binding to and neutralizing the pathological form of the prion protein (PrP^Sc), thus interfering with prion disease progression and toxicity. Our research aims to employ the evolutionary conserved cleavages of the prion protein for therapeutic purposes to fight devastating neurodegenerative conditions such as Creutzfeldt-Jakob Disease.