Prions and their partners in crime

Abstract

Prions, the infectious agents of transmissible spongiform encephalopathies (TSEs), have defied full characterization for decades. The dogma has been that prions lack nucleic acids and are composed of a pathological, self-inducing form of the host's prion protein (PrP). Recent progress in propagating TSE infectivity in cell-free systems has effectively ruled out the involvement of foreign nucleic acids. However, host-derived nucleic acids or other non-PrP molecules seem to be crucial. Interactions between TSE-associated PrP and its normal counterpart are also pathologically important, so the physiological functions of normal PrP and how they might be corrupted by TSE infections have been the subject of recent research.

Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells

“…The experiment was repeated four times (Luhr et al 2002(Luhr et al , 2004 our model used peripheral primary neurons that were infected in vivo after oral scrapie challenge (Beekes and McBride 2007). Thus our model speciWcally targeted a cell-to-cell transmission of PrP Sc (Caughey and Baron 2006) from the immune system to the PNS, hypothetically at the genesis of the prion peripheral neuroinvasion (Kimberlin and Walker 1989). In this purpose, the dissemination of prions via infected apoptotic cells or cellular fragments was limited by frequent washing.…”

“…These structures, referred to as tunneling nanotubes (TNT) were shown to facilitate the transport of various cellular components (Rustom et al 2004). Some authors have hypothesized that some small pathogens, such as prions, can be disseminated by these exchange processes (Caughey and Baron 2006;Gousset et al 2009). Several arguments attest of the implication of TNT in prions spreading.…”

Disease‐associated prion protein is not detectable in human systemic amyloid deposits

“…In many forms of TSE, the PrP Sc deposits contain typical amyloid fibrils and the deposits share the pathognomonic tinctorial features of amyloid [5], but TSE pathology and clinical features of TSE can exist in both animals and humans in the absence of any detectable amyloid deposits [6,7]. Nevertheless, all, or nearly all, forms of TSE are associated with the accumulation of PrP Sc [2][3][4], although the precise molecular PrP conformations associated with infectivity are still poorly defined [8]. PrP Sc in tissues is best demonstrated by immunohistochemistry, using validated methods that minimize the staining of normal PrP C and enhance the staining of PrP Sc [4].…”

The saga of prion: to cut or not to cut

“…In contrast, the normal physiologic function of PrP C remains an enigma [5][6][7]. Human PrP C is a highly conserved, relatively small (209 amino acid long), glycophos-phatidylinositol (GPI) anchored cell surface protein.…”

“…A myriad of proteins have been reported to bind PrP C ; these proteins include cell surface proteins, secreted proteins, cytoplasmic proteins as well as nuclear proteins. In addition, PrP C also binds lipids, glycosaminoglycans, nucleic acids as well as divalent cations, such as copper, zinc and iron [5][6][7]. As a GPI-anchored cell surface glycoprotein, PrP C resides in lipid rafts, which are micro-domains on the cell surface and are important in signal transduction [8].…”