Prion processing: a double-edged sword? Available to Purchase

The events leading to the degradation of the endogenous PrP^C (normal cellular prion protein) have been the subject of numerous studies. Two cleavage processes, α-cleavage and β-cleavage, are responsible for the main C- and N-terminal fragments produced from PrP^C. Both cleavage processes occur within the N-terminus of PrP^C, a region that is significant in terms of function. α-Cleavage, an enzymatic event that occurs at amino acid residues 110 and 111 on PrP^C, interferes with the conversion of PrP^C into the prion disease-associated isoform, PrP^Sc (abnormal disease-specific conformation of prion protein). This processing is seen as a positive event in terms of disease development. The study of β-cleavage has taken some surprising turns. β-Cleavage is brought about by ROS (reactive oxygen species). The C-terminal fragment produced, C2, may provide the seed for the abnormal conversion process, as it resembles in size the fragments isolated from prion-infected brains. There is, however, strong evidence that β-cleavage provides an essential process to reduce oxidative stress. β-Cleavage may act as a double-edged sword. By β-cleavage, PrP^C may try to balance the ROS levels produced during prion infection, but the C2 produced may provide a PrP^Sc seed that maintains the prion conversion process.