Molecular pathogenesis of prion diseases

Prion diseases such as Creutzfeldt-Jakob disease in humans, scrapie in shee p, and BSE in cattle are transmissible sind fatal neurodegenerative disease s. The infectious agent of these diseases has been designated as "prion'". It consists mainly and perhaps exclusively of a conformational Variant of a physiological glycoprotein, the cellular prion, protein, PrPC, which is a copper-binding protein of the cell surface. In spite of the wealth of bioch emical and biophysical information, the conformational transition from PrPC to PrPSc, the infectious isoform of the prion protein, is not well underst ood. Nerve cell loss in prion diseases may be caused by neurotoxic effects of the prion protein. Certain properties of the prion protein such as the a pparent form of its glycosylation and conformational properties reflected b y the preferential site of digestion with proteinase K are associated with particular phe notypes of prion disease. The appearance of a new variant of Creutzfeldt-Jakob disease in humans, which is most likely caused by the co nsumption of BSE-infected food in the UK, is cause for major concern partic ularly since there is no known effective treatment of prion diseases.