Review: Creutzfeldt-Jakob disease: prion protein type, disease phenotype and agent strain.
ABSTRACT 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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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.Virus Research 10/2014; · 2.83 Impact Factor
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ABSTRACT: The essential involvement of water in most fundamental extra-cellular and intracellular processes of proteins is critically reviewed and evaluated in this article. The role of water in protein behavior displays structural ambivalence; it can protect the disordered peptide-chain by hydration or helps the globular chain-folding, but promotes also the protein aggregation, as well (see: diseases). A variety of amyloid diseases begins as benign protein monomers but develops then into toxic amyloid aggregates of fibrils. Our incomplete knowledge of this process emphasizes the essential need to reveal the principles of governing this oligomerization. To understand the biophysical basis of the simpler in vitro amyloid formation may help to decipher also the in vivo way. Nevertheless, to ignore the central role of the water's effect among these events means to receive an uncompleted picture of the true phenomenon. Therefore this review represents a stopgap role, because the most published studies—with a few exceptions—have been neglected the crucial importance of water in the protein research. The following questions are discussed from the water's viewpoint: (i) interactions between water and proteins, (ii) protein hydration/dehydration, (iii) folding of proteins and miniproteins, (iv) peptide/protein oligomerization, and (v) amyloidosis. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.Journal of Peptide Science 08/2014; · 1.86 Impact Factor
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ABSTRACT: Creutzfeldt-Jakob disease (CJD) is a rare but lethal prion disease. The worldwide mortality rate of CJD is 1.67 per one million people, although 90% of cases will lead to death within one year of symptom onset. Rapid, progressive dementia is the cardinal sign of CJD. Other early symptoms include deterioration of muscle coordination, memory, judgment, and vision, as well as personality changes, insomnia, and depression. It occurs in two types, classic and new variant, and classic CJD can be further divided into three subtypes: sporadic, familial (ie, genetic), and iatrogenic (ie, health care associated). Surgery often requires using instruments that come in contact with high-infectivity tissue, especially during neurosurgical procedures and diagnostic biopsies. To reduce the risk of disease transmission, infection control practices should include identification of the risk of infection, implementation of safety protocols (eg, use of personal protective equipment), proper selection and use of instrumentation, and adequate disinfection and sterilization practices. Silent carriers, risks of iatrogenic infection, and the possibility of inadvertent exposure of healthy patients may carry great liability to public health and hospital stability.AORN journal 10/2014; 100(4):390-410.