Figure 1.

The chaperone, cyclophilin B is critical for the proper maturation of the prion protein (PrP) and of presenilin 1. The substitution of proline 102 or 105 leads to PrP misfolding, aggregation and deposition in cytosolic aggresomes, resulting in the development of the Gerstmann-Sträussler-Scheinker syndrome. Similarly, the substitution of proline in residues 264 or 267 of presenilin 1 prevents cyclophilin B from assisting its folding, causing aggregation, deposition in the ER and loss of γ secretase function. This impairs mitochondrial distribution and activity, as well as other cellular functions and underlies the manifestation of certain cases of familial Alzheimer's disease.