Scrapie and Cellular Prion Proteins Differ in Their Kinetics of Synthesis and Topology in Cultured Cells

Borchelt, David R.; Scott, Michael J.; Taraboulos, Albert; Stahl, N.; Prusiner, S. B.

doi:10.1097/00005072-199005000-00156

Cited by 96 publications

(149 citation statements)

References 26 publications

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

“…Thus, and although PrP Sc has a glycosylphosphatidylinositol (GPI) anchor [134], the manner in which PrP Sc associates with membranes differs from that of PrP C and has yet to be determined. While PrP C is rapidly synthesised and degraded [14,23,97,100], the abnormal form is much more stable. Earlier pulse-chase experiments did not yield evidence that infected cells could eliminate PrP Sc [14,25].…”

Section: Cell Models Propagating Naturally-occurring Prion Isolatesmentioning

confidence: 99%

“…While PrP C is rapidly synthesised and degraded [14,23,97,100], the abnormal form is much more stable. Earlier pulse-chase experiments did not yield evidence that infected cells could eliminate PrP Sc [14,25]. Experiments blocking prion multiplication with anti PrP antibodies later showed that infected N2a cells do get rid of PrP Sc [41,44,102,104].…”

Section: Cell Models Propagating Naturally-occurring Prion Isolatesmentioning

confidence: 99%

See 1 more Smart Citation

Cell models of prion infection

Vilette

2007

Vet. Res.

View full text Add to dashboard Cite

-Due to recent renewal of interest and concerns in prion diseases, a number of cell systems permissive to prion multiplication have been generated in the last years. These include established cell lines, neuronal stem cells and primary neuronal cultures. While most of these models are permissive to experimental, mouse-adapted strains of prions, the propagation of natural field isolates from sheep scrapie and chronic wasting disease has been recently achieved. These models have improved our knowledge on the molecular and cellular events controlling the conversion of the PrP C protein into abnormal isoforms and on the cell-to-cell spreading of prions. Infected cultured cells will also facilitate investigations on the molecular basis of strain identity and on the mechanisms that lead to neurodegeneration. The ongoing development of new cell models with improved characteristics will certainly be useful for a number of unanswered critical issues in the prion field.

show abstract

Section: Cell Models Propagating Naturally-occurring Prion Isolatesmentioning

confidence: 99%

Section: Cell Models Propagating Naturally-occurring Prion Isolatesmentioning

confidence: 99%

Cell models of prion infection

Vilette

2007

Vet. Res.

View full text Add to dashboard Cite

show abstract

“…Although the majority of PrP Sc generated in infected animals contains a GPI anchor, soluble forms of PrP released from the cell surface are GPI deficient and observed in murine neuroblastoma or in mice cell culture [9,14,15] or directly in mice brains [91]. Besides in scrapie-infected cells the absence of the GPI anchor reduces conversion [102], which suggests that conversion involves membranebound GPI-anchored PrP.…”

Section: Conversion Of Prions Is Likely To Occur At the Membrane Surfacementioning

confidence: 99%

“…It is now widely accepted, although not definitely proven, that the infective agent is the PrP itself according to the so-called "proteinonly hypothesis" [95] . Strong evidence indicates that the conversion of a normal soluble α-helical monomeric protein into a β-sheetrich oligomeric structure and further fibrillar aggregation are the key events in the disease pathogenesis [9,90]. To distinguish between these two conformers of the same protein, the terms PrP C and PrP Sc are used to name respectively the endogenous non-pathogenic form and the disease-associated isoform.…”

Section: Introductionmentioning

confidence: 99%

Misfolding of the prion protein: linking biophysical and biological approaches

2008

View full text Add to dashboard Cite

-Prion diseases are a group of neurodegenerative diseases that can arise spontaneously, be inherited, or acquired by infection in mammals. The propensity of the prion protein to adopt different structures is a clue to its pathological and perhaps biological role too. While the normal monomeric PrP is well characterized, the misfolded conformations responsible for neurodegeneration remain elusive despite progress in this field. Both structural dynamics and physico-chemical approaches are thus fundamental for a better knowledge of the molecular basis of this pathology. Indeed, multiple misfolding pathways combined with extensive posttranslational modifications of PrP and probable interaction(s) with cofactors call for a combination of approaches. In this review, we outline the current physico-chemical knowledge explaining the conformational diversities of PrP in relation with postulated or putative cellular partners such as proteic or non-proteic ligands.

show abstract

“…The normal or cellular form of the prion protein (PrP c) is expressed in many tissues in the body, but is detected at highest levels in neurons within the central nervous system [2]. PrP c has a short half-life, and is soluble and easily degraded by proteolytic enzymes [5]. In prion diseases, an abnormal isoform of PrP (designated PrP Sc ) accumulates in the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

Variant Creutzfeldt–Jakob disease and its transmission by blood

Ironside

Head

2003

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Summary. Variant Creutzfeldt–Jakob disease (vCJD) is a novel acquired human prion disease resulting from human exposure to the agent causing bovine spongiform encephalopathy (BSE). vCJD differs from all other human prion diseases in that the disease‐associated form of the prion protein and infectivity are present in lymphoid tissues throughout the body. Lymphoid tissues and lymphocytes are implicated in the peripheral pathogenesis of prion diseases (where infectivity may be detected during the preclinical phase of the illness), giving rise to concerns that blood and blood products may also contain infectivity, thus representing a possible source of iatrogenic spread of vCJD. These concerns have been reinforced by the recent transmission of BSE in an experimental sheep model by blood transfusion from an infected animal in the preclinical phase of the illness. Studies in other animal models suggest that most infectivity in blood may be cell‐associated, with lower levels in the plasma, and there is evidence to indicate that any infectivity present may be reduced during the process of plasma fractionation. At present, the attempts to detect disease‐associated prion protein and infectivity in buffy coat from vCJD patients have been negative, but these studies have been limited in size and in the sensitivity of the detection systems employed. Further studies are required to develop more sensitive means of detection of disease‐associated prion protein in blood; such techniques could also be employed for screening purposes, both individually and to help ascertain more precisely the likely numbers of future cases of vCJD.

show abstract

Scrapie and Cellular Prion Proteins Differ in Their Kinetics of Synthesis and Topology in Cultured Cells

Cited by 96 publications

References 26 publications

Cell models of prion infection

Cell models of prion infection

Misfolding of the prion protein: linking biophysical and biological approaches

Variant Creutzfeldt–Jakob disease and its transmission by blood

Contact Info

Product

Resources

About