Molecular biology of prion diseases

  title={Molecular biology of prion diseases},
  author={Stanley B. Prusiner},
  pages={1515 - 1522}
Prions cause transmissible and genetic neurodegenerative diseases, including scrapie and bovine spongiform encephalopathy of animals and Creutzfeldt-Jakob and Gerstmann-Straussler-Scheinker diseases of humans. Infectious prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein, which is encoded by a chromosomal gene. A posttranslational process, as yet unidentified, converts the cellular prion protein into an abnormal isoform. Scrapie incubation times… 

Natural and experimental prion diseases of humans and animals

Transgenetic investigations of prion diseases of humans and animals.

  • S. Prusiner
  • Biology
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences
  • 1993
Investigations of prion diseases using transgenesis promise to yield much new information about these once enigmatic disorders.

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.

Human prion diseases

The prion diseases, sometimes referred to as the “transmissible spongiform encephalopathies,” include kuru, Creutzfeldt‐Jakob disease, and Gerstmann‐Sträussler‐Scheinker disease of humans as well as

Neurodegeneration in humans caused by prions.

Prion diseases include kuru, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia of humans as well as scrapie and bovine spongiform encephalopathy of

Molecular biology and pathogenesis of prion diseases.

  • S. Prusiner
  • Medicine, Biology
    Trends in biochemical sciences
  • 1996

Deciphering Prion Diseases with Transgenic Mice

Despite intensive searches over the past three decades, no nucleic acid has been found within prions, yet a modified isoform of the host-encoded PrP designated PrPSc is essential for infectivity.

Human prion diseases and bovine spongiform encephalopathy (BSE).

Molecular analysis of prion strains suggests that new variant Creutzfeldt-Jakob disease is caused by BSE exposure, and the novel biology of prions propagation may not be unique to these rare degenerative brain diseases.

Molecular and Genetic Basis of Prion Diseases

Despite intensive searches over the past three decades, no nucleic acid has been found within prions; yet, a modified isoform of the host-encoded PrP designated PrPSc is essential for infectivity.



Inherited human prion diseases

Transmission of CJD and scrapie to rodents and primates produce strikingly similar clinical and neuropathologic characteristic and there is nearly 90% conservation of amino acid sequence among hamster, mouse, and human PrP molecule form the basis for concluding that prions cause kuru, CJD, and GSS in humans.

Linkage of a prion protein missense variant to Gerstmann–Sträussler syndrome

It is shown here that PrP codon 102 is linked to the putative gene for the syndrome in two pedigrees, providing the best evidence to date that this familial condition is inherited despite also being infectious, and that substitution of leucine for proline at PrPcodon 102 may lead to the development of Gerstmann–Sträussler syndrome.

Spontaneous neurodegeneration in transgenic mice with mutant prion protein

Many of the clinical and pathological features of Gerstmann-Straussler-Scheinker syndrome are reproduced in transgenic mice containing a prion protein with a single amino acid substitution, illustrating that a neurodegenerative process similar to a human disease can be genetically modeled in animals.

Molecular cloning of a human prion protein cDNA.

The conservation between the hamster and human prion proteins suggests that they may have an important role in cellular metabolism and may explain the similarities between scrapie and CJD.

Scrapie prion proteins are synthesized in neurons.

The authors found that prion proteins are synthesized almost exclusively within neurons, and the finding of PrP mRNA in neurons may explain the degeneration and vacuolation that occurs in these cells during scrapie infection.

Human prion protein cDNA: molecular cloning, chromosomal mapping, and biological implications.

The extensive homology of this gene sequence to the hamster PrP 27- to 30-kilodalton prion protein complementary DNA clone, and its existence as a single copy in the human genome, leads to the conclusion that this is the human prion gene.

Two alleles of a neural protein gene linked to scrapie in sheep.

Two sheep genomic DNA clones are isolated that encode proteins of 256 amino acids with high homology to the PrPs of other species that may be related to the alleles of the scrapie incubation-control gene in this species.

Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins

Scrapie and Creutzfeldt-Jakob disease are transmissible, degenerative neurological diseases caused by prions. Considerable evidence argues that prions contain protease-resistant sialoglycoproteins,

Assignment of the human and mouse prion protein genes to homologous chromosomes.

These results should lead to studies of genetic loci syntenic with the PrP gene, which may play a role in the pathogenesis of prion diseases or other degenerative neurologic disorders.

Creutzfeldt-Jakob disease prion proteins in human brains.

The findings suggest that the amyloid plaques found in the brains of patients with Creutzfeldt-Jakob disease may be composed of paracrystalline arrays of prions similar to those in prion diseases in laboratory animals.