Cell adhesion can trigger a signal transduction pathway implicating PrP that leads to neurite outgrowth and neuronal survival. In addition we believe that oxidative stress could by itself trigger PrP mediated signalling. This is inferred from a study on PrP cleavage. In fact it is commonly assumed that the physiological isoform of prion protein, PrPC, is cleaved during its normal processing between residues 111/112, whereas the pathogenic isoform, PrPSc, is cleaved at an alternate site in the octapeptide repeat region around position 90. We demonstrated both in cultured cells and in vivo, that PrPC is subject to a complex set of post-translational processing with the molecule being cleaved upstream of position 111/112, in the octapeptide repeat region or at position 96. PrP has therefore two main cleavage sites that we decided to name alpha and beta. Cleavage of PrPC at these sites leads us to postulate that PrP this processing is involved in the function of PrP in defence to oxidative stress.

Ref : Mangé, A., Béranger, F., Peoc'h, K., Onodera, T., Frobert, Y. & Lehmann S. (2004) Alpha- and beta- cleavages of the amino-terminus of the cellular prion protein. Biology of the Cell 96, 125-32.