PATHOLOGICAL CONFORMATIONS OF PRION PROTEINS

While many aspects of prion disease biology are unorthodox, perhaps th e most fundamental paradox is posed by the coexistence of inherited, s poradic, and infectious forms of these diseases. Sensible molecular me chanisms for prion propagation must explain all three forms of prion d iseases in a manner that is compatible with the formidable array of ex perimental data derived from histopathological, biochemical, biophysic al, human genetic, and transgenetic studies. In this review, we explor e prion disease pathogenesis initially from the perspective of an auto somal dominant inherited disease. Subsequently, we examine how an intr insically inherited disease could present in sporadic and infectious f orms. Finally, we explore the phenomenologic constraints on models of prion replication with a specific emphasis on biophysical studies of p rion protein structures.