Prions: protein only or something more? Overview of potential prion cofactors.
Transmissible spongiform encephalopathies (TSEs) in humans and animals are attributed to protein-only infectious agents, called prions. Prions have been proposed to arise from the conformational conversion of the cellular protein PrP(C) into a misfolded form (e.g., PrP(Sc) for scrapie), which precipitates into aggregates and fibrils. It has been proposed that the conversion process is triggered by the interaction of the infectious form (PrP(Sc)) with the cellular form (PrP(C)) or might result from a mutation in the gene for PrP(C). However, until recently, all efforts to reproduce this process in vitro had failed, suggesting that host factors are necessary for prion replication. In this review we discuss recent findings such as the cellular factors that might be involved in the conformational conversion of prion proteins and the potential mechanisms by which they could operate.
Fasano
Carlo
C
Unité de Trafic Membranaire et Pathogénése, Institut Pasteur, 75724 Paris Cedex 15, France.
Campana
Vincenza
V
Zurzolo
Chiara
C
D000818:Animals; D001923:Brain Chemistry; D002474:Cell-Free System; D004705:Endocytosis / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D018832:Molecular Chaperones / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010447:Peptide Hydrolases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D018621:PrPC Proteins / Q000737:chemistry / Q000502:physiology; D018620:PrPSc Proteins / Q000737:chemistry; D017096:Prion Diseases / Q000209:etiology / Q000503:physiopathology / Q000662:veterinary; D011328:Prions / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D011480:Protease Inhibitors; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D012608:Scrapie / Q000378:metabolism; D012995:Solubility
D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions; D011480:Protease Inhibitors; D010447:Peptide Hydrolases