What veterinary practitioners should know about scrapie

Bulgin, Marie S.; Melson, Sharon Sorensen

doi:10.2460/javma.230.8.1158

Cited by 4 publications

(1 citation statement)

References 50 publications

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“…The structure of the PrP Sc strain in the inoculum would be transmitted upon conversion of host PrP C to PrP Sc [14] . While over 20 different strains of sheep scrapie have been identified in the UK, the diversity of strains present in the US sheep population is not as well-characterized [15] , and the level of diversity may be underestimated by the standard, non-transgenic mouse bioassay [16] . Since sheep hosts of different PRNP genotypes differ in their level of susceptibility to isolates of scrapie [1] , and scrapie eradication efforts are based on breeding genetics, a better understanding of the properties of the different strains will enhance options for control and eradication of scrapie.…”

Section: Introductionmentioning

confidence: 99%

Relationships between PrPSc Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System

et al. 2012

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Transmissible spongiform encephalopathies (TSEs), including scrapie in sheep (Ovis aries), are fatal neurodegenerative diseases caused by the misfolding of the cellular prion protein (PrPC) into a â-rich conformer (PrPSc) that accumulates into higher-order structures in the brain and other tissues. Distinct strains of TSEs exist, characterized by different pathologic profiles upon passage into rodents and representing distinct conformations of PrPSc. One biochemical method of distinguishing strains is the stability of PrPSc as determined by unfolding in guanidine hydrochloride (GdnHCl), which is tightly and positively correlated with the incubation time of disease upon passage into mice. Here, we utilize a rapid, protease-free version of the stability assay to characterize naturally occurring scrapie samples, including a fast-acting scrapie inoculum for which incubation time is highly dependent on the amino acid at codon 136 of the prion protein. We utilize the stability methodology to identify the presence of two distinct isolates in the inoculum, and compare isolate properties to those of a host-stabilized reference scrapie isolate (NADC 13-7) in order to assess the stability/incubation time correlation in a natural host system. We demonstrate the utility of the stability methodology in characterizing TSE isolates throughout serial passage in livestock, which is applicable to a range of natural host systems, including strains of bovine spongiform encephalopathy and chronic wasting disease.

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Section: Introductionmentioning

confidence: 99%

Relationships between PrPSc Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System

et al. 2012

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Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

2010

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Exposure to a variety of toxins and/or infectious agents leads to disease, degeneration and death, often characterised by circumstances in which cells or tissues do not merely die and cease to function but may be more or less entirely obliterated. It is then legitimate to ask the question as to whether, despite the many kinds of agent involved, there may be at least some unifying mechanisms of such cell death and destruction. I summarise the evidence that in a great many cases, one underlying mechanism, providing major stresses of this type, entails continuing and autocatalytic production (based on positive feedback mechanisms) of hydroxyl radicals via Fenton chemistry involving poorly liganded iron, leading to cell death via apoptosis (probably including via pathways induced by changes in the NF-κB system). While every pathway is in some sense connected to every other one, I highlight the literature evidence suggesting that the degenerative effects of many diseases and toxicological insults converge on iron dysregulation. This highlights specifically the role of iron metabolism, and the detailed speciation of iron, in chemical and other toxicology, and has significant implications for the use of iron chelating substances (probably in partnership with appropriate anti-oxidants) as nutritional or therapeutic agents in inhibiting both the progression of these mainly degenerative diseases and the sequelae of both chronic and acute toxin exposure. The complexity of biochemical networks, especially those involving autocatalytic behaviour and positive feedbacks, means that multiple interventions (e.g. of iron chelators plus antioxidants) are likely to prove most effective. A variety of systems biology approaches, that I summarise, can predict both the mechanisms involved in these cell death pathways and the optimal sites of action for nutritional or pharmacological interventions.

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Diseases of the Nervous System

2017

Veterinary Medicine

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The tenth edition of this deservedly popular book marks its coming of age, but in spite of the widespread changes in neurological concepts and ideas since 1940, it remains essentially a practical handbook for general practitioners and students. An interesting innovation in the present edition is a chapter on liverbrain relationships. In it, Dr John Walshe describes with clarity the effects of primary liver disease on the central nervous system, and the biochemical and neurological effects of such metabolic disorders as

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What veterinary practitioners should know about scrapie

Cited by 4 publications

References 50 publications

Relationships between PrPSc Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System

Relationships between PrPSc Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

Diseases of the Nervous System

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