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Alternatives to animal bioassays for prions
- Source :
- Michael Beekes
- Publication Year :
- 2014
-
Abstract
- Bioassays that involve the use of laboratory animals are often considered to be the ‘gold standard’ for the detection and titration of certain pathogens. This holds particularly true for prions,1,2 which are the proteinaceous infectious particles that cause fatal neurodegenerative diseases in animals (e.g. scrapie, bovine spongiform encephalopathy [BSE]) and humans (e.g. sporadic or variant Creutzfeldt–Jakob disease [sCJD, vCJD]). The BSE epidemic and resulting emergence of vCJD in the United Kingdom, and the subsequent occurrence of BSE and vCJD in other countries, have substantially increased the worldwide awareness of prions and their potential risk to public health. Unlike bacteria, viruses or fungi, prions are pathogens that are devoid of coding nucleic acids. According to the prion hypothesis, they consist essentially of a misfolded and aggregated isoform of the host-encoded prion protein (PrP).1 Prion-forming conformers of the prion protein are referred to as PrPSc or PrPTSE (‘Sc’ and ‘TSE’ are acronyms for scrapie, and transmissible spongiform encephalopathy, respectively, with the latter being an alternative name for prion diseases).1,3 The replication of prions shows close similarities to the seeded growth of crystals, and is thought to occur by a mechanism of nucleation-dependent PrP polymerisation,4,5 i.e. oligomers or polymers of PrPTSE act as nuclei (‘seeds’) that recruit cellular prion protein (PrPC) and incorporate it, in a misfolded form, into their own aggregate structure. When PrPTSE aggregates eventually fall apart into smaller units, this causes a multiplication of PrP particles with proteinaceous seeding activity, and thereby a further autocatalytic replication of the pathological protein state. According to this concept, the self-replication of prions is based on their biochemical seeding activity, i.e. the ability to convert cellular protease-sensitive prion protein into misfolded, aggregated and often Proteinase K (PK)-resistant PrP (PrPres). Prion bioassays and the Three Rs
- Subjects :
- Transmissible spongiform encephalopathy
Potential risk
Prions
animal diseases
Bovine spongiform encephalopathy
Scrapie
General Medicine
Biology
Toxicology
medicine.disease
Proteinase K
Animal Testing Alternatives
Virology
General Biochemistry, Genetics and Molecular Biology
nervous system diseases
Medical Laboratory Technology
Aggregate structure
medicine
biology.protein
Nucleic acid
Bioassay
Animals
Biological Assay
Subjects
Details
- ISSN :
- 02611929
- Volume :
- 41
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Alternatives to laboratory animals : ATLA
- Accession number :
- edsair.doi.dedup.....642177c89aee7d0d7b057d7f0a76e6e6