Clinical research
Prion diseases, what are they? By Professor Jean Manson, Prof RG Will and Prof Andrew Smith
Prions and dentistry
T
he prion diseases (or transmissible spongiform encepha- lopathies) belong to a group of diseases
known as the protein misfolding diseases. This group also includes diseases such as Alzheimer’s and Parkinson’s disease. In these diseases, a normal host protein does not assume its normal func- tional structure but is described as misfolding and as such accumulates in large deposits in the brain. In prion diseases, the protein
which misfolds is known as the prion protein (PrPC) and the misfolded form PrPSc. These diseases typi- cally have a very long asymptomatic phase during which the protein accumulates in the brain and there is a gradual loss of neurones and neuronal function. This results, finally, in a relatively short clinical phase with a variety of clinical symptoms depending on which region of the brain is affected. The folding and misfolding path-
ways of a protein are very complex and result in many different forms of the protein. Which of these forms is involved in the death of neurones is not known. It is, however, known that the host protein is central to the disease as removal of the PrPC in animal models leads to a total resistance to prion diseaseı, 2. Prion diseases are set apart
from the other protein misfolding diseases, as they are known to be infectious. This was first demon- strated as early as ı936, when the
56 Scottish Dental magazine
prion disease in sheep known as sheep scrapie was shown to be experimentally transmitted between sheep3. Infection has since been demon- strated for a variety of prion diseases of both animals and humans by transmission to animal models4, 5. Importantly, although diseases in animals had been recorded for more than 200 years, there was never any evidence prior to ı996 of prion disease in animals transmitting to humans6, 7. Moreover, while many prion diseases have been shown to be infectious, it is not certain that all prion diseases are infectious8. The nature of the infectious
agent has been proposed to be the misfolded form of the prion protein known as PrPSc9. There is, however, no certainty over which form of the misfolded protein is infectious or whether indeed other compo- nents are required to render the protein infectious. Prion diseases can pass from
individual to individual within a species and on occasions have been shown to pass from one species to another. However, there is a major barrier for transmission between speciesı0, which is in part, but not solely, dependent on the differences in prion protein from species to speciesıı. This ‘species barrier’ is likely to
explain the relatively low numbers of variant Creutzfeld-Jakob disease (vCJD) in the human population
when compared with the very large number of cases of bovine spongi- form encephalopathy (BSE) and the widespread exposure of the human population to BSE-infected meat products. However, the implemen- tation of regulations preventing the highly infected tissues from entering the food chainı2 were also likely to have been important in containing the epidemic. The current position of the vCJD epidemic is described below.
vCJD – the current position Variant CJD was identified in ı9966 and the hypothesis that this novel human disease was caused by BSE has been supported by a range of epidemiological and laboratory evidence. Notably, transmission studies in animal models have demonstrated that the prion strain in vCJD is the same as that causing BSE and different from the prion strains in other human prion disease such as sporadic CJD7. Risk factors for vCJD include resi-
dence in the UK, dietary exposure to foodstuffs containing high levels of BSE infectivity and a specific genetic
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