Grand ideas floating freely

Prion protein (PrP) is critically involved in the transmission and pathogenesis of the transmissible spongiform encephalopathies (TSEs), which include scrapie in sheep, variant and sporadic Creutzfeldt–Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE) in cattle. The normal, cellular PrPc protein encoded by the Prnp gene is required for susceptibility to TSE. The interconversion of this normal form into the highly protease-resistant PrPSc conformation leads to the formation of PrP aggregates and amyloid fibrils in the brain and ultimately to neurodegeneration in the affected animal. It has been proposed that this abnormal form of PrP is itself the infectious agent of transmission; however, this matter remains unsettled for a variety of reasons (Chesebro, 1998, 1999). The topics covered during this meeting included the structure and function of PrP, TSE pathogenesis, new efforts towards diagnostic tests, and the normal and abnormal roles of the newly described ‘doppel’ protein in gametogenesis and neurodegeneration.