The state of the prion

@article{Weissmann2004TheSO,
  title={The state of the prion},
  author={Charles Weissmann},
  journal={Nature Reviews Microbiology},
  year={2004},
  volume={2},
  pages={861-871}
}
  • C. Weissmann
  • Published 1 November 2004
  • Biology, Medicine
  • Nature Reviews Microbiology
There is little doubt that the main component of the transmissible agent of spongiform encephalopathies — the prion — is a conformational variant of the ubiquitous host protein PrPC, and that the differing properties of various prion strains are associated with different abnormal conformations of this protein. The precise structure of the prion is not yet known, nor are the mechanisms of infection, conformational conversion and pathogenesis understood. 

Figures and Topics from this paper

Molecular mechanisms of human prion diseases
TLDR
Prions are both infectious and neurotoxic, and recent evidence suggests that these properties segregate with distinct molecular forms of this protein. Expand
Birth of a Prion: Spontaneous Generation Revisited
TLDR
This work shows that the agent, the prion, can be replicated in a cell-free system, that it can be generated de novo, and that the strain-specific properties of prions are encoded by conformational variations of the underlying protein. Expand
Prions of Vertebrates
TLDR
Detailed clinical, pathological, and molecular data from a large number of human prion disease patients indicate that phenotypic diversity in humanPrion disease relates to the propagation of disease-related prion protein isoforms with distinct physicochemical properties. Expand
Differential Epitope-Mapping of the Two Forms of the Prion Protein: Alterations at the C-Terminus
Most of the diagnostic methods for transmissible spongiform encephalopathies are based on the detection of the abnormal protease-resistant conformers of the prion protein (PrPSc), when the normalExpand
Role of lipid in forming an infectious prion?
TLDR
The literature regarding the chemical nature of the infectious agent and the potential contribution from lipid molecules to prion infectivity is reviewed, and the important remaining questions in this research area are discussed. Expand
The Structure of Human Prions: From Biology to Structural Models — Considerations and Pitfalls
TLDR
The general background related to prion biology is discussed and the structural models proposed to date are assessed, while highlighting the experimental challenges of elucidating the structure of PrPSc. Expand
Thoughts on mammalian prion strains.
A plethora of prion strains can be propagated indefinitely in hosts homozygous for the PrP gene. Within the framework of the "protein-only" hypothesis, the strain-specific properties are encipheredExpand
Copper and the prion protein: methods, structures, function, and disease.
  • G. Millhauser
  • Chemistry, Medicine
  • Annual review of physical chemistry
  • 2007
TLDR
Recent connections between copper and PrP(C) are described, with an emphasis on the electron paramagnetic resonance elucidation of the specific copper-binding sites, insights into PrP (C) function, and emerging connections between Copper and prion disease. Expand
Intriguing nucleic-acid-binding features of mammalian prion protein.
TLDR
The participation of NAs in prion propagation opens new avenues for developing new diagnostic tools and therapeutics to target prion diseases, as well as for understanding the function of PrP(C), probably as a NA chaperone. Expand
Prions of Vertebrates
TLDR
The principles of protein conformation-based inheritance established from studying mammalian prions are of far wider relevance in human disease, and the emerging and rapidly developing field of protein-misfolding diseases has prion disease as a key paradigm. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 129 REFERENCES
A 'unified theory' of prion propagation
There is now very persuasive evidence that the transmissible agent for spongiform encephalopathies such as scrapie, consists of a modified form of the normal host protein PrPc, devoid of any nucleicExpand
Transmission of prions.
The "protein only" hypothesis holds that the infectious agent causing transmissible spongiform encephalopathies is a conformational isomer of PrP, a host protein that is predominantly expressed inExpand
Prion replication and secondary nucleation.
  • L. Orgel
  • Biology, Medicine
  • Chemistry & biology
  • 1996
The infectious agents responsible for the prion diseases appear to be aggregates of a modified form of the prion protein, PrPSc, that grow at the expense of the normal form, PrPC. The mechanism ofExpand
Conversion of PrP to a Self-Perpetuating PrPSc-like Conformation in the Cytosol
TLDR
It is reported that PrP retrogradely transported out of the endoplasmic reticulum produced both amorphous aggregates and a PrPSc-like conformation in the cytosol, and the distribution between these forms correlated with the rate of appearance in the Cytosol. Expand
Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD
TLDR
Strain characteristics revealed here suggest that the prion protein may itself encode disease phenotype, consistent with BSE being the source of this new disease. Expand
Transmission of the BSE Agent to Mice in the Absence of Detectable Abnormal Prion Protein
TLDR
Although all of the mice injected with homogenate from BSE-infected cattle brain exhibited neurological symptoms and neuronal death, more than 55 percent had no detectable PrPres, suggesting that a further unidentified agent may actually transmit BSE. Expand
Prion Protein and the Transmissible Spongiform Encephalopathy Diseases
TLDR
Further understanding of the structure of PrP-res and of amyloids in similar diseases, such as Alzheimer's disease, may provide clues as to the differences and similarities among these protein folding diseases. Expand
Evidence for the Conformation of the Pathologic Isoform of the Prion Protein Enciphering and Propagating Prion Diversity
TLDR
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. Expand
Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein
TLDR
It is now feasible to determine whether mice devoid of PrPc can propagate prions and are susceptible to scrapie pathogenesis. Expand
A transmembrane form of the prion protein in neurodegenerative disease.
TLDR
Aberrant regulation of protein biogenesis and topology at the endoplasmic reticulum can result in neurodegeneration. Expand
...
1
2
3
4
5
...