Chaperones of Mammals

The crucial event in prion diseases involves the conformational change of the cellular form of the prion protein into the pathogenic isoform. This change causes a dramatic alteration within the structure. Structural 

The protein-only hypothesis indicates that the scrapie form of the prion protein can promote the conversion of the cellular form. This leads to the conclusion that prions themselves can act as chaperones (Liautard, 1991). Thermokinetic analysis of protein folding shows that a misfolded chaperone gives rise to new misfolded chaperones, which fit very well to the protein-only hypothesis in which PrP triggers the formation of PrP.  

Besides this theory, other proteins can act as promotors for the prion conversion reaction. In 1996 chemical reagents were investigated and were shown to affect formation and propagation of PrP. Cellular osmolytes and proteinaceous chaperones were tested in this context (Tatzelt et al., 1996b). Chaperones that can prevent the formation of PrpSc (Fig. 4) might act as powerful tools for the generation of anti-TSE therapeutics. 

Molecular chaperones also represent a biochemical and mechanisti-cal link between the mammalian prions and the prion-like proteins in 

Studies on the transmission of human prion proteins to transgenic mice indicate the existance of an unknown protein termed protein X , which binds to PrP (Telling et al, 1995) and might act as a molecular chaperone. 

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