HYPOTHESIS - THE MEETING PLACE MODEL FOR PRION DISEASE

Prions are responsible for spongiform diseases such as scrapie and bov ine spongiform encephalopathy. It is now generally accepted that the d isease mechanism involves the conversion from the normal form, PrPC, t o the pathogenic form, PrPSc, and that this isoform is infectious. In the case of scrapie, 15 different forms of the disease have been descr ibed and some of these different phenotypes can be conferred by infect ious prions that are themselves encoded by normal genes. We propose he re that a prion with an altered structure has a correspondingly altere d preference for lipids; this altered preference creates a proteolipid domain containing different lipid and other factors such as chaperoni ns and enzymes responsible for post-translational modifications. Norma l prions associated with this abnormal domain adopt the conformation d ictated by its lipidic composition (and by the other factors present) and so acquire the lipidic preference of the original pathogenic prion s. There transformed prions could then create new proteolipid domains. This process may be considered as semi-conservative replication in wh ich prion and lipids are analogous to the Watson and Crick strands and the proteolipid domain to the double helix itself.