The cellular prion protein (PrPC) plays important roles in neurodegenerative diseases. First, it is the well-established substrate for the conformational conversion into its pathogenic isoform (PrPSc) giving rise to progressive and fatal prion diseases. Moreover, several recent reports highlight important roles of PrPC in other neurodegenerative conditions such as Alzheimer's disease. Since PrPC is subject to proteolytic processing, here we discuss the two main cleavage events under physiological conditions, α-cleavage and shedding. We focus on how these cleavages and the resulting fragments may impact prion diseases as well as other neurodegenerative proteinopathies. Finally, we discuss the recently identified sheddase of PrPC, namely the metalloprotease ADAM10, with regard to therapeutic potential against neurodegenerative diseases.
Besides its role in fatal and transmissible prion diseases, the cellular prion protein seems to play central roles in other neurodegenerative diseases. Here, the physiological proteolytic cleavage of this protein is reviewed with a focus on how this might influence neurodegenerative conditions, such as prion diseases and Alzheimer's disease.