The cellular and pathologic prion protein

The cellular prion protein, PrPC, is a small, cell-surface glycoprotein with a function that is currently somewhat ill-defined. It is also the key molecule involved in the family of neurodegenerative disorders called transmissible spongiform encephalopathies, which are also known as prion diseases. The misfolding of PrPC to a conformationally-altered isoform, designated PrPSc, is the main molecular process involved in pathogenesis and appears to precede many other pathological and clinical manifestations of disease, including neuronal loss, astrogliosis and cognitive loss. PrPSc is also believed to be the major component of the infectious “prion”, the agent responsible for disease transmission, and preparations of this protein can cause prion disease when inoculated into a naïve host. Thus, understanding the biochemical and biophysical properties of both PrPC and PrPSc, and ultimately the mechanisms of their interconversion, are critical if we are to understand prion disease biology. Although entire books could be devoted to research pertaining to the protein, herein we briefly review the state of knowledge of prion biochemistry, including consideration of prion protein structure, function, misfolding and dysfunction.