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 PrPTSE, is the main molecular process involved in pathogenesis and appears to precede many other pathologic and clinical manifestations of disease, including neuronal loss, astrogliosis, and cognitive loss. PrPTSE 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 PrPTSE, and ultimately the mechanisms of their interconversion, is 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.
Keywords: PRNP; amyloid; cofactors; conformational conversion; glycosylation; membrane anchor; misfolding; prion function; prion protein; toxicity.
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