ÐÇ¿Õ´«Ã½

The prion protein, a normal cellular protein, is suspected to be a major, if not the only component of the agent that causes the spongiform encephalopathies. During the course of these diseases, the prion protein is "converted" to a protease-resistant form. It is this protease-resistant form that has been attributed with pathogenic potential. Two of these diseases, Creutzfeldt-Jakob disease (CJD) and the recently described fatal familial insomnia (FFI), are propagated as inherited or sporadic forms. The inherited form of FFI shares a mutation of codon 178 of the protein gene with one type of inherited CJD. We have shown that the genetic basis for these two diseases arising from a single mutation lies in a common polymorphism in the prion protein gene. The polymorphism apparently affects the topography of the lesions produced in the two diseases. Since the conformation of the prion protein seems to be at the heart of the pathogenic process, our group is trying to characterize the effect of known mutations in the prion protein gene on the synthesis and metabolism of the protein which result in a variety of distinct neurodegenerative conditions in both cell and animal models. We are also investigating the disease process at a cellular level.