Synthetic Mammalian Prions

  title={Synthetic Mammalian Prions},
  author={Giuseppe Legname and Ilia V. Baskakov and Hoang-Oanh B. Nguyen and Detlev Riesner and Fred E. Cohen and Stephen J. DeArmond and Stanley B. Prusiner},
  pages={673 - 676}
Recombinant mouse prion protein (recMoPrP) produced in Escherichia coli was polymerized into amyloid fibrils that represent a subset of β sheet–rich structures. Fibrils consisting of recMoPrP(89–230) were inoculated intracerebrally into transgenic (Tg) mice expressing MoPrP(89–231). The mice developed neurologic dysfunction between 380 and 660 days after inoculation. Brain extracts showed protease-resistant PrP by Western blotting; these extracts transmitted disease to wild-type FVB mice and Tg… 

Protease-Sensitive Synthetic Prions

It is reported here that protease-sensitive, synthetic prions were generated in vitro during polymerization of recombinant (rec) PrP into amyloid fibers, demonstrating that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrPSc.

Spontaneous and BSE-prion-seeded amyloid formation of full length recombinant bovine prion protein.

Convergent replication of mouse synthetic prion strains.

Infectious prions and proteinopathies

It is shown that inoculation of rec-PrP fibrils does not always cause clinical TSE disease or increased infectious titre, but can seed the formation of PrP amyloid plaques in PrP-P101L knock-in transgenic mice (101LL).

Synthetic prions with novel strain-specified properties

A large number of amyloid preparations were able to induce the conformational change of endogenous PrPC to harbor several distinctive proteinase-resistant PrP forms, and one such preparation was characterized in vivo habouring a synthetic prion with novel strain specified neuropathological and biochemical properties.

Generating a Prion with Bacterially Expressed Recombinant Prion Protein

Recombinant prion protein recapitulates the characteristics of the infectious agent in prion disease and is resistant to proteinase-K, but also shows infectivity in cultured cells and causes rapid disease progression in wild-type mice, yielding both the behavioral and the neuropathological symptoms.

In Vitro Generation of Infectious Scrapie Prions

De novo generation of prion strains

Several recent studies are discussed that have produced an array of novel prion strains in vitro that exhibit increasingly high titres of infectivity and promise unprecedented insight into the structure of prions and the mechanisms by which they originate and propagate.

Structure of mammalian prions

Pieced together, these data present PrPSc as a stackable molecule whose core is probably a β-solenoid formed by two or three rungs of short β-strands interspersed with numerous loops and turns, and a reasonable understanding of its architecture might soon be achieved.

Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins

The data show that novel TSE agents can be generated de novo solely from purified mouse rPrP after amplification in mice coexpressing normal levels of wt and anchorless PrPC and suggest that the PrPC GPI anchor can modulate the propagation of synthetic TSE strains.



Strain-specified characteristics of mouse synthetic prions.

The incubation times, neuropathological lesion profiles, and Gdn1/2 values indicate that MoSP1 prions differ from RML and many other prion strains derived from sheep with scrapie and cattle with bovine spongiform encephalopathy.

Self-assembly of recombinant prion protein of 106 residues.

Following the conformational transition, rPrP106 possesses properties similar to those of PrP(Sc)106, such as high beta-sheet content, defined tertiary structure, resistance to limited digestion by proteinase K, and high thermodynamic stability.

Evidence for the Conformation of the Pathologic Isoform of the Prion Protein Enciphering and Propagating Prion Diversity

The results presented indicate that the conformation of PrP sc functions as a template in directing the formation of nascent PrPSc and suggest a mechanism to explain strains of prions where diversity is encrypted in the conformed PrP Sc.

A synthetic peptide initiates Gerstmann-Sträussler-Scheinker (GSS) disease in transgenic mice.

It is concluded that a chemically synthesized peptide refolded into the appropriate conformation can accelerate or possibly initiate prion disease.

Protease-resistant prion protein produced in vitro lacks detectable infectivity.

It is argued that acquisition of protease resistance by PrP(C) is not sufficient for the propagation of infectivity, and MH2M PrP was produced in vitro, and no infectivity was detected on bioassay.

Neurotoxicity of a prion protein fragment

It is reported here that neuronal death results from chronic exposure of primary rat hippocampal cultures to micromolar concentrations of a peptide corresponding to residues 106–126 of the amino-acid sequence deduced from human PrP complementary DNA.

Prion diseases of humans and animals: their causes and molecular basis.

The appearance of a novel human prion disease, variant CJD, and the clear experimental evidence that it is caused by exposure to BSE has highlighted the need to understand the molecular basis of prion propagation, pathogenesis, andThe barriers limiting intermammalian transmission.

Identification of Two Prion Protein Regions That Modify Scrapie Incubation Time

Evidence is provided that the N terminus of MoPrP and the chimeric region of MHM2 PrP both influence the inherent efficiency of prion propagation.