Review: Creutzfeldt-Jakob disease: Prion protein type, disease phenotype and agent strain

National CJD Research & Surveillance Unit, School of Molecular & Clinical Medicine, University of Edinburgh, Edinburgh, UK.
Neuropathology and Applied Neurobiology (Impact Factor: 3.93). 03/2012; 38(4):296-310. DOI: 10.1111/j.1365-2990.2012.01265.x
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M. W. Head and J. W. Ironside (2012) Neuropathology and Applied Neurobiology38, 296–310
Creutzfeldt–Jakob disease: prion protein type, disease phenotype and agent strain
The human transmissible spongiform encephalopathies or human prion diseases are one of the most intensively investigated groups of rare human neurodegenerative conditions. They are generally held to be unique in terms of their complex epidemiology and phenotypic variability, but they may also serve as a paradigm with which other more common protein misfolding disorders might be compared and contrasted. The clinico-pathological phenotype of human prion diseases appears to depend on a complex interaction between the prion protein genotype of the affected individual and the physico-chemical properties of the neurotoxic and transmissible agent, thought to comprise of misfolded prion protein. A major focus of research in recent years has been to define the phenotypic heterogeneity of the recognized human prion diseases, correlate this with molecular-genetic features and then determine whether this molecular-genetic classification of human prion disease defines the biological properties of the agent as determined by animal transmission studies. This review seeks to survey the field as it currently stands, summarize what has been learned, and explore what remains to be investigated in order to obtain a more complete scientific understanding of prion diseases and to protect public health.

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    • "Familial CJD (fCJD), Gerstmann–Sträussler–Scheinker disease (GSS), fatal familial insomnia (FFI) and prion protein cerebral amyloid angiopathy (PrP-CAA) are genetic forms of human TSE. The acquired forms are transmitted from human to human, as iatrogenic CJD (iCJD) and Kuru; or from cattle to human, as variant CJD (vCJD) (Head and Ironside, 2012). In animals, relevant TSE are scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle, and chronic wasting disease (CWD) in cervids (Imran and Mahmood, 2011). "
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    ABSTRACT: Transmissible spongiform encephalopathies (TSE) are a heterogeneous group of neurodegenerative disorders. The common feature of these diseases is the pathological conversion of the normal cellular prion protein (PrP(C)) into a β-structure-rich conformer-termed PrP(Sc). The latter can induce a self-perpetuating process leading to amplification and spreading of pathological protein assemblies. Much evidence suggests that PrP(Sc) itself is able to recruit and misfold PrP(C) into the pathological conformation. Recent data have shown that recombinant PrP(C) can be misfolded in vitro and the resulting synthetic conformers are able to induce the conversion of PrP(C) into PrP(Sc)in vivo. In this review we describe the state-of-the-art of the body of literature in this field. In addition, we describe a cell-based assay to test synthetic prions in cells, providing further evidence that synthetic amyloids are able to template conversion of PrP into prion inclusions. Studying prions might help to understand the pathological mechanisms governing other neurodegenerative diseases. Aggregation and deposition of misfolded proteins is a common feature of several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and other disorders. Although the proteins implicated in each of these diseases differ, they share a common prion mechanism. Recombinant proteins are able to aggregate in vitro into β-rich amyloid fibrils, sharing some features of the aggregates found in the brain. Several studies have reported that intracerebral inoculation of synthetic aggregates lead to unique pathology, which spread progressively to distal brain regions and reduced survival time in animals. Here, we review the prion-like features of different proteins involved in neurodegenerative disorders, such as α-synuclein, superoxide dismutase-1, amyloid-β and tau. Copyright © 2014. Published by Elsevier B.V.
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    • "Variant CJD is a novel human transmissible spongiform encephalopathy transmitted by the consumption of tissues from cattle affected by bovine spongiform encephalopathy (BSE) (Head & Ironside, 2012). The latter is a disease of cattle that resulted from feeding the animals with meat and bone meal. "
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