Synthetic Prions

Eiden, Martin; Buschmann, A.; Kupfer, Leila; Groschup, Martin H.

doi:10.1111/j.1439-0450.2006.00966.x

Cited by 10 publications

(4 citation statements)

References 52 publications

(62 reference statements)

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“…Ovine PrP genotypes, which are not susceptible to classical scrapie in vivo also failed to be converted to PrP res in vitro . Another cell-free assay in which bacterially expressed PrP C was co-incubated with PrP Sc from mouse scrapie brains [ 63 ] was used to demonstrate that a single amino acid substitution within a mouse-ovine chimeric PrP C results in an inconvertible mutant of the previous convertible molecule [ 64 ].…”

Section: Effects Of the Primary Structure Of Prion Protein On Its Mismentioning

confidence: 99%

Prion Protein Misfolding

Kupfer

Hinrichs²,

Groschup³

2009

CMM

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The crucial event in the development of transmissible spongiform encephalopathies (TSEs) is the conformational change of a host-encoded membrane protein - the cellular PrPC - into a disease associated, fibril-forming isoform PrPSc. This conformational transition from the α-helix-rich cellular form into the mainly β-sheet containing counterpart initiates an ‘autocatalytic’ reaction which leads to the accumulation of amyloid fibrils in the central nervous system (CNS) and to neurodegeneration, a hallmark of TSEs.The exact molecular mechanisms which lead to the conformational change are still unknown. It also remains to be brought to light how a polypeptide chain can adopt at least two stable conformations. This review focuses on structural aspects of the prion protein with regard to protein-protein interactions and the initiation of prion protein misfolding. It therefore highlights parts of the protein which might play a notable role in the conformational transition from PrPC to PrPSc and consequently in inducing a fatal chain reaction of protein misfolding. Furthermore, features of different proteins, which are able to adopt insoluble fibrillar states under certain circumstances, are compared to PrP in an attempt to understand the unique characteristics of prion diseases.

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Section: Effects Of the Primary Structure Of Prion Protein On Its Mismentioning

confidence: 99%

Prion Protein Misfolding

Kupfer

Hinrichs²,

Groschup³

2009

CMM

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“…All are associated with the conversion of a normal host cellular protein, the prion protein (PrP C ), into a misfolded disease-associated form, PrP Sc , which accumulates in the central nervous system (CNS) [29]. The prion hypothesis states that PrP Sc is the principal (if not the sole) component of the transmissible agents responsible for this group of diseases [30]; this hypothesis is supported by an increasing body of experimental evidence [9]. However, the precise relationship between the conformation of PrP Sc in different forms of prion disease and the biological properties of the transmissible agents (strain characteristics) in different prion diseases is still unresolved.…”

Section: Introductionmentioning

confidence: 99%

UK Iatrogenic Creutzfeldt–Jakob disease: investigating human prion transmission across genotypic barriers using human tissue-based and molecular approaches

et al. 2016

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Creutzfeldt–Jakob disease (CJD) is the prototypic human prion disease that occurs most commonly in sporadic and genetic forms, but it is also transmissible and can be acquired through medical procedures, resulting in iatrogenic CJD (iCJD). The largest numbers of iCJD cases that have occurred worldwide have resulted from contaminated cadaveric pituitary-derived human growth hormone (hGH) and its use to treat primary and secondary growth hormone deficiency. We report a comprehensive, tissue-based and molecular genetic analysis of the largest series of UK hGH-iCJD cases reported to date, including in vitro kinetic molecular modelling of genotypic factors influencing prion transmission. The results show the interplay of prion strain and host genotype in governing the molecular, pathological and temporal characteristics of the UK hGH-iCJD epidemic and provide insights into the adaptive mechanisms involved when prions cross genotypic barriers. We conclude that all of the available evidence is consistent with the hypothesis that the UK hGH-iCJD epidemic resulted from transmission of the V2 human prion strain, which is associated with the second most common form of sporadic CJD.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-016-1638-x) contains supplementary material, which is available to authorized users.

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“…Another assay was published which dealt with aggregation and fibrillation of recombinant prion protein in the absence of PrP Sc seeds [20]. However, the infectious nature of the so-called "synthetic prions" still remains enigmatic [21]. …”

Section: Introductionmentioning

confidence: 99%

Effects of polymorphisms in ovine and caprine prion protein alleles on cell-free conversion

Eiden

Soto

Mettenleiter

et al. 2011

Vet Res

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In sheep polymorphisms of the prion gene (PRNP) at the codons 136, 154 and 171 strongly influence the susceptibility to scrapie and bovine spongiform encephalopathy (BSE) infections. In goats a number of other gene polymorphisms were found which are suspected to trigger similar effects. However, no strong correlation between polymorphisms and TSE susceptibility in goats has yet been obtained from epidemiological studies and only a low number of experimental challenge data are available at present. We have therefore studied the potential impact of these polymorphisms in vitro by cell-free conversion assays using mouse scrapie strain Me7. Mouse scrapie brain derived PrPSc served as seeds and eleven recombinant single mutation variants of sheep and goat PrPC as conversion targets. With this approach it was possible to assign reduced conversion efficiencies to specific polymorphisms, which are associated to low frequency in scrapie-affected goats or found only in healthy animals. Moreover, we could demonstrate a dominant-negative inhibition of prion polymorphisms associated with high susceptibility by alleles linked to low susceptibility in vitro.

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Synthetic Prions

Cited by 10 publications

References 52 publications

Prion Protein Misfolding

Prion Protein Misfolding

UK Iatrogenic Creutzfeldt–Jakob disease: investigating human prion transmission across genotypic barriers using human tissue-based and molecular approaches

Effects of polymorphisms in ovine and caprine prion protein alleles on cell-free conversion

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