Prion diseases: current understanding of epidemiology and pathogenesis, and therapeutic advances.

CEA-National TSE Reference Laboratory, Istituto Zooprofilattico Sperimentale del Piemonte, Turin, Italy.
CNS Drugs (Impact Factor: 5.11). 02/2006; 20(1):15-28.
Source: PubMed


The bovine spongiform encephalopathy (BSE) epidemic, along with the related threat to human health posed by the transmission of the BSE agent to humans, has highlighted the importance of prion diseases. These fatal neurodegenerative diseases are characterised by spongiform changes in the CNS, and comprise a wide spectrum of clinicopathological entities in humans and animals, such as Creutzfeldt-Jakob disease (CJD) and its emerging new variant (vCJD) in humans, and BSE and scrapie in animals. This article reviews the geographical distribution and the temporal trends of CJD and vCJD; the major events in the pathogenesis of prion diseases; the risk factors for sporadic CJD and vCJD; and the possible strategies for treating them. Worldwide statistics indicate that sporadic CJD has a stable incidence of one case per million people per year; in contrast, the incidence of vCJD appears to have increased exponentially from its characterisation in 1994 to a peak in 2000. As of December 2005, 183 definite or probable cases of vCJD had been reported worldwide. The crucial event in the pathogenesis of prion diseases is the conversion of the normally occurring cellular prion protein (PrP(c)) into a pathogenic form, called protease-resistant PrP (PrP(res)) or scrapie PrP (PrP(sc)). Pathogenetic studies in rodent models have shown that PrP(sc) is found in the enteric nervous system and in the gut-associated lymphoid tissue following oral scrapie ingestion. The role of the lymphoreticular system in the pathogenesis of TSE seems to be related to the strains of agents and the host genotype. Therapeutic approaches to vCJD are mainly based on the inhibition or prevention of the pathological change that creates PrP(sc). Derivatives of acridine (such as mepacrine [quinacrine]) and the phenothiazine psychotropics have been proposed as possible therapies because of their activity in cellular models; however, neither class was able to affect the protease resistance of preexisting PrP fibrils. More encouragingly, in animal models of prion disease, tetracyclines were found to reduce prion infectivity by direct inactivation of PrP(sc). While these findings are promising, the suitability of these compounds for clinical use is still limited by their low efficacy once symptoms are apparent. Treatments based on the vaccination approach have also produced positive results, but further investigations are necessary to establish their clinical application.

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Available from: Giuseppe Ru, Jul 15, 2014
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    • "Methods (2009), doi:10.1016/j.mimet.2009.01.017 varies depending on the nature of the infective strain, the route of transmission, and the genetic susceptibility of the recipient. This has led to the fear that an unknown proportion of the population who have been eating potentially contaminated meat in the 1980s might currently present as asymptomatic carriers of the vCJD infectious agent, despite current statistics which indicate that the number of deaths by vCJD peaked in 2000 and has been in decline since (Caramelli et al., 2006; Setbon et al., 2005). Beside transmission of the infectious agent through the ingestion of contaminated products, bearing in mind the potential threat of vCJD incubating in the population, a number of medical procedures are now also considered as posing a potential risk of iatrogenic contamination with PrP Sc (Pana and Jung, 2005; Lumley and Serious Hazards of Transfusion Committee, 2008). "
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    ABSTRACT: Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases with no cure to this day, and are often associated with the accumulation of amyloid plaques in the brain and other tissues in affected individuals. The emergence of new variant Creutzfeldt-Jakob disease, an acquired TSE with a relatively long asymptomatic incubation period and unknown prevalence or incidence, which could potentially be iatrogenically transmitted, has prompted the need for sensitive and rapid methods of detection of the pathology indicator, the protease-resistant prion protein (PrP(Sc)), in tissues and on surgical instruments. To discriminate between common tissue proteins and amyloid-rich aggregates such as those formed by abnormal prion, we developed a quantitative thioflavin T/SYPRO Ruby dual staining procedure, used in combination with episcopic differential interference contrast/epifluorescence (EDIC/EF) microscopy for rapid scanning of samples. The detection limit of this direct observation technique applied to brain homogenates was greatly enhanced by the addition of Tween 20, as demonstrated in double-blind studies using various proportions of ME7-infected brain mixed with normal brain homogenate. The characteristic thioflavin T signal correlated with the relative amount of prion amyloid and proved at least 2-log more sensitive than the classic Western blot using the same prepared samples. This new sensitive microscopy procedure, which can be easily applied in instrument decontamination surveys, is likely to be more sensitive that Western blot in practice since it does not rely on the elution of resilient PrP(Sc) bound to the instrument surfaces. Our study also demonstrates how interactions between prion and lipid-rich tissue homogenates may reduce the sensitivity of such detection assays.
    Full-text · Article · Feb 2009 · Journal of microbiological methods
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    • "At this time, the epidemiological evidence suggest that among animal TSEs only cattle BSE has been transmitted to humans, generating a variant form of CJD (vCJD) (Bruce, 2000; Collinge, 1999; Ironside and Head, 2004). It is unlikely that sheep scrapie is a concern for humans, because the disease has been described for centuries and no increased prevalence of human prion diseases has been found in scrapie endemic areas (Caramelli et al., 2006; Hunter, 1998). However, the appearance on new " atypical " strains of scrapie as well as the known transmission of BSE to sheep has generated new concerns of human infections with sheep-derived material (Buschmann and Groschup, 2005; Hunter, 2003). "
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