Evolving views in prion glycosylation: functional and pathological implications

Prion diseases form a group of neurodegenerative disorders with the unique feature of being transmissible. These diseases involve a pathogenic protein, called PrPSc for the scrapie isoform of the cellular prion protein (PrPC) which is an abnormally-folded counterpart of PrPC. Many questions remain unresolved concerning the function of PrPC and the mechanisms underlying prion replication, transmission and neurodegeneration. PrPc is a glycosyl-phosphatidylinositol-anchored glycoprotein expressed at the cell surface of neurons and other cell types. PrPC may be present as distinct isoforms depending on proteolytic processing (full length and truncated), topology(GPI-anchored, transmembrane or soluble) and glycosylation (non- mono- and di-glycosylated). The present review focuses on the implications of PrPC glycosylation, as to the function of the normal protein, the cellular pathways of conversion into PrPSc, the diversity of prion strains and the related selective neuronal targeting. (C) 2003 Editions scientifiques et medicales Elsevier SAS and Societe francaise de biochimie et biologic moleculaire. All rights reserved.