FIGURE 2.

Schematic representation of the corruption of PrP^c-mediated signaling in prion-infected cells. PrP^Sc accumulation is associated with the constitutive recruitment of various effectors of PrP^c, including the Fyn kinase, the MAP kinases ERK1/2 and the CREB transcription factor. Prion-infected cells also exhibit recruitment of the stress-associated kinases p38 and JNK, which mirrors oxidative stress conditions. A downstream event in this cascade is the drastic reduction in MMP-9 mRNAs and activity, which, in turn, causes an impairment in Aβ clearance, leading to Aβ accumulation. Aβ oligomers would bind PrP^c and possibly PrP^Sc and further fuel the activation of this signaling cascade, thereby sustaining a vicious circle.