Search results for "Scrapie"

Kinetics of expression of prion protein in uninfected and scrapie-infected N2a mouse neuroblastoma cells.

1993

The scrapie prion protein, PrPSc, is formed from its isoform, the cellular PrPc. There is evidence available indicating that PrPSc is necessary component of the infectious prion particle to cause a series of transmissible spongiform encephalopathies. We have used immunocytochemistry and RNA blotting techniques to investigate if infection with prions results in an increased PrP gene expression. For the experiments we used N2a cells which had been infected with prions (ScN2a cells). We demonstrated by confocal laser scanning microscopy that PrP-protein was present in the nucleus (predominantly in the nucleoli) of ScN2a cells. Analysis of the PrP-mRNA levels both in N2a- and in ScN2a cells usi…

Glycosylation deficiency at either one of the two glycan attachment sites of cellular prion protein preserves susceptibility to bovine spongiform enc…

2004

The conversion into abnormally folded prion protein (PrP) plays a key role in prion diseases. PrP(C) carries two N-linked glycan chains at amino acid residues 180 and 196 (mouse). Previous in vitro data indicated that the conversion process may not require glycosylation of PrP. However, it is conceivable that these glycans function as intermolecular binding sites during the de novo infection of cells on susceptible organisms and/or play a role for the interaction of both PrP isoforms. Such receptor-like properties could contribute to the formation of specific prion strains. However, in earlier studies, mutations at the glycosylation sites of PrP led to intracellular trafficking abnormalitie…

Prion protein gene frequencies in three Sicilian dairy sheep populations

2008

The objective of this paper was to investigate the prion protein (PrP) genotype and haplotype frequencies in three Sicilian dairy sheep populations. The three populations were: (1) 1096 Valle del Belice animals, (2) 1143 Comisana animals, and (3) 1771 individuals from 5 flocks with scrapie outbreaks, in which the animals were crossbreds derived from indigenous Sicilian dairy breeds. PrP genotypes are described for the three codons 136 (Alanine or Valine; A, V), 154 (Histidine or Arginine; H, R), and 171 (Glutamine, Arginine or Histidine; Q, R, H) which represent polymorphisms known to be linked with scrapie susceptibility. The Valle del Belice haplotype frequencies were 32.3% ARR, 6.5% AHQ,…

PrP Gene Polymorphism in Medieval Remains of Sicilian Sheep

2015

Encephalopathy in sheep was at first described in Ireland in 1732 and was called scrapie. Ancient DNA in archaeogenetics represents an effective method to evaluate the ancestral pedigree of living animals and track evolutionary changes occurred between the past and the present day. Since several point mutations are today widely described in modern scrapie, no data about both sequence and frequency are still available for the prion protein (PrP) gene in ancient breeds. In order to evaluate whether the haplotypes distribution in ancient sheep differed from those of the modern population we evaluated polymorphism at four well know codons of the Prp Open Reading Frame. In the present work, we c…

Two novel amino acid substitutions in highly conserved regions of prion protein (PrP) and a high frequency of a scrapie protective variant in native …

2019

Background Polymorphisms of the prion protein gene may influence scrapie susceptibility in small ruminants through modified protein conformation. At least 47 amino acid substitutions and 19 silent polymorphisms have been described in goat PRNP reported from several countries. The objective of this study was to investigate PRNP polymorphisms of native Ethiopian goat breeds and compare the results with other goat breeds. Results The analysis of the prion protein gene PRNP in 229 goats belonging to three of the main Ethiopian native goat breeds showed a remarkably high frequency (> 34.6%) of p.(Asn146Ser) in these breeds, a variant involved in scrapie resistance in Cyprus. In addition, two nov…

Indagini archeozoologiche della Palermo antica: la Gancia, Palazzo Bonagia e Via Imera.

L’analisi archeozoologica della Palermo medioevale qui presentata si inserisce nell’ambito degli studi di antropologia e di archeologia medievale che da oltre un decennio stanno interessando il centro storico della città. Il presente studio mira alla ricostruzione dell’ecologia umana durante il periodo di islamizzazione della Sicilia e di Palermo, attraverso l’analisi dei resti faunistici di tre siti inediti del centro storico di Palermo, la Gancia, Palazzo Bonagia e Via Imera, in un periodo compreso tra la fine del IX e il X sec. d.C., e l’analisi comparativa di resti provenienti da centri rurali siciliani, alcuni di questi databili fino al XV secolo. L’analisi ha messo in evidenza alcuni …

Mathematical models for the diffusion magnetic resonance signal abnormality in patients with prion diseases

2014

In clinical practice signal hyperintensity in the cortex and/or in the striatum on magnetic resonance (MR) diffusion-weighted images (DWIs) is a marker of sporadic Creutzfeldt–Jakob Disease (sCJD). MR diagnostic accuracy is greater than 90%, but the biophysical mechanisms underpinning the signal abnormality are unknown. The aim of this prospective study is to combine an advanced DWI protocol with new mathematical models of the microstructural changes occurring in prion disease patients to investigate the cause of MR signal alterations. This underpins the later development of more sensitive and specific image-based biomarkers. DWI data with a wide a range of echo times and diffusion weightin…

Prions, mad cow disease, and preventive measures: a critical appraisal

2003

In 1996 the first key epidemiological study on bovine spongiform encephalitis (BSE) appeared in the renowned journal Nature [1]. In that article it was estimated that by the year 1996, some 750,000 cows with BSE had entered the food chain in Great Britain. Accordingly, millions of people in GB must have consumed contaminated meat. That same year the first report on a new form of Creutzfeldt-Jakob disease [variant (v) CJD] manifesting in young patients appeared [26]. A connection between this disease and BSE was assumed. In view of the suspicion that the use of meat and bone meal (MBM) had led to the outbreak of BSE, feeding with MBM was banned in the year 1988. The number of new BSE infecti…

Novel approaches in diagnosis and therapy of Creutzfeldt-Jakob disease.

2000

The scrapie prion protein, PrP(Sc), as well as its peptide fragment, PrP106-126, are toxic on neuronal cells, resulting in cell death by an apoptotic, rather than necrotic mechanism. The apoptotic process of neuronal cells induced by prion protein supports diagnosis and offers potential targets for therapeutic intervention of the prion diseases. Among the cerebrospinal fluid (CSF) proteins, which may serve as markers of neuronal cell death associated with prion diseases, the 14-3-3 protein(s) turned out to be the most promising one. A new sensitive assay allows the detection of even small changes in the normally low levels of these proteins. In vitro, the toxic effects displayed by PrP(Sc) …

Neuroprotective effect of flupirtine in prion disease

2003

Apoptotic neuronal cell death is a hallmark of prion diseases. The apoptotic process in neuronal cells is thought to be caused by the scrapie prion protein, PrPSc, and can be experimentally induced by its peptide fragment, PrP106-126. This process is a target for potential drugs to combat prion disease or to ameliorate its symptoms. Flupirtine (Katadolon), a pyridine derivative that is in clinical use as a nonopioid analgesic, has a potent cytoprotective effect, at concentrations above 1 microg/mL, on neuronal cells treated with PrP(Sc) or PrP106-126. This drug acts as an N-methyl-D-aspartate (NMDA) antagonist, but does not bind to NMDA receptors. Flupirtine normalizes the level of intracel…