scholarly journals Neuropathology of Animal Prion Diseases

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 466
Author(s):  
Leonor Orge ◽  
Carla Lima ◽  
Carla Machado ◽  
Paula Tavares ◽  
Paula Mendonça ◽  
...  
Keyword(s):  
Prion Diseases ◽  
Clinical Signs ◽  
Small Ruminants ◽  
Neuronal Loss ◽  
Cellular Prion Protein ◽  
Brain Inflammation ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Spongiform Encephalopathies ◽  
Lesion Profile

Transmissible Spongiform Encephalopathies (TSEs) or prion diseases are a fatal group of infectious, inherited and spontaneous neurodegenerative diseases affecting human and animals. They are caused by the conversion of cellular prion protein (PrPC) into a misfolded pathological isoform (PrPSc or prion- proteinaceous infectious particle) that self-propagates by conformational conversion of PrPC. Yet by an unknown mechanism, PrPC can fold into different PrPSc conformers that may result in different prion strains that display specific disease phenotype (incubation time, clinical signs and lesion profile). Although the pathways for neurodegeneration as well as the involvement of brain inflammation in these diseases are not well understood, the spongiform changes, neuronal loss, gliosis and accumulation of PrPSc are the characteristic neuropathological lesions. Scrapie affecting small ruminants was the first identified TSE and has been considered the archetype of prion diseases, though atypical and new animal prion diseases continue to emerge highlighting the importance to investigate the lesion profile in naturally affected animals. In this report, we review the neuropathology and the neuroinflammation of animal prion diseases in natural hosts from scrapie, going through the zoonotic bovine spongiform encephalopathy (BSE), the chronic wasting disease (CWD) to the newly identified camel prion disease (CPD).

scholarly journals Susceptibility of Cattle to First-passage Intracerebral Inoculation with Chronic Wasting Disease Agent from White-tailed Deer

2007 ◽  
Vol 44 (4) ◽  
pp. 487-493 ◽  
Author(s):  
A. N. Hamir ◽  
J. M. Miller ◽  
R. A. Kunkle ◽  
S. M. Hall ◽  
J. A. Richt
Keyword(s):  
Chronic Wasting Disease ◽  
Prion Diseases ◽  
Clinical Signs ◽  
Diagnostic Techniques ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Spongiform Encephalopathies ◽  
Disease Agent ◽  
Sheep Scrapie

Fourteen, 3-month-old calves were intracerebrally inoculated with the agent of chronic wasting disease (CWD) from white-tailed deer (CWDwtd) to compare the clinical signs and neuropathologic findings with those of certain other transmissible spongiform encephalopathies (TSE, prion diseases) that have been shown to be experimentally transmissible to cattle (sheep scrapie, CWD of mule deer [CWDmd], bovine spongiform encephalopathy [BSE], and transmissible mink encephalopathy). Two uninoculated calves served as controls. Within 26 months postinoculation (MPI), 12 inoculated calves had lost considerable weight and eventually became recumbent. Of the 12 inoculated calves, 11 (92%) developed clinical signs. Although spongiform encephalopathy (SE) was not observed, abnormal prion protein (PrPd) was detected by immunohistochemistry (IHC) and Western blot (WB) in central nervous system tissues. The absence of SE with presence of PrPd has also been observed when other TSE agents (scrapie and CWDmd) were similarly inoculated into cattle. The IHC and WB findings suggest that the diagnostic techniques currently used to confirm BSE would detect CWDwtd in cattle, should it occur naturally. Also, the absence of SE and a distinctive IHC pattern of CWDwtd and CWDmd in cattle suggests that it should be possible to distinguish these conditions from other TSEs that have been experimentally transmitted to cattle.

Human Prion Diseases

2013 ◽  
pp. 149-160
Author(s):  
James W. Ironside ◽  
Matthew P. Frosch ◽  
Bernardino Ghetti
Keyword(s):  
Prion Diseases ◽  
Neuronal Loss ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Pituitary Hormone ◽  
Human Pituitary ◽  
Spongiform Encephalopathies ◽  
Jakob Disease ◽  
Prnp Codon ◽  
Codon 129

This chapter describes and illustrates the neuropathology of prion diseases, also known as transmissible spongiform encephalopathies. These diseases are characterized pathologically by varying combinations of spongiform change, neuronal loss, reactive gliosis, and prion protein (PrP) deposition. The morphologic pattern depends on the etiology of the disease and the genotype of the patient. Different clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (CJD) have been described depending on the PRNP codon 129 genotype and the PrP isotype. A novel form known as variably protease-sensitive prionopathy has been recently identified. Familial prion diseases include familial CJD, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. Over 40 different PRNP mutations have been identified. Acquired prion diseases include Kuru; iatrogenic CJD, particularly in recipients of contaminated human pituitary hormone, and variant CJD, which seems closely related to bovine spongiform encephalopathy.

scholarly journals Diagnosis of Transmissible Spongiform Encephalopathies in Animals: A Review

2005 ◽  
Vol 17 (6) ◽  
pp. 509-527 ◽  
Author(s):  
Dolores Gavier-Widén ◽  
Michael J. Stack ◽  
Thierry Baron ◽  
Aru Balachandran ◽  
Marion Simmons
Keyword(s):  
Prion Diseases ◽  
Small Ruminants ◽  
Immunohistochemical Analysis ◽  
Considerable Effect ◽  
Proteinase K ◽  
Screening Tests ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Spongiform Encephalopathies ◽  
Prion Strain

Transmissible spongiform encephalopathies (TSEs) in animals include, among others, bovine spongiform encephalopathy (BSE), scrapie, chronic wasting disease, and atypical forms of prion diseases. Diagnosis of TSEs is based on identification of characteristic lesions or on detection of the abnormal prion proteins in tissues, often by use of their partial proteinase K resistance property. Correctly sampling of target tissues is of utmost importance as this has a considerable effect on test sensitivity. Most of the rapid or screening tests are based on ELISA or Western immunoblot (WB) analysis, and many are officially approved. Confirmatory testing is normally performed by use of histologic examination, immunohistochemical analysis, certain WB protocols, or detection of prion fibrils by use of electron microscopy (scrapie-associated fibril). The discriminatory methods for diagnostic use are mostly based on WB technology and provide initial identification of the prion strain, particularly for differentiation of BSE from scrapie in small ruminants. Definitive prion strain characterization is performed by use of bioassays, usually in mice. A burgeoning number of transgenic mice have been developed for TSE studies. Development of new tests with higher sensitivity and of more reliable diagnostic applications for live animals tested for food safety reasons is a rapidly developing field. Ultimately, the choice of a test for TSE diagnosis depends on the rationale for the testing.

scholarly journals Mechanisms of prion-induced neurodegeneration

2016 ◽  
Vol 18 ◽  
Author(s):  
Paula Saá ◽  
David A. Harris ◽  
Larisa Cervenakova
Keyword(s):  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Neuronal Loss ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Therapeutic Approaches ◽  
Spongiform Encephalopathies ◽  
Membrane Bound ◽  
The Brain

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders characterised by long incubation period, short clinical duration, and transmissibility to susceptible species. Neuronal loss, spongiform changes, gliosis and the accumulation in the brain of the misfolded version of a membrane-bound cellular prion protein (PrPC), termed PrPTSE, are diagnostic markers of these diseases. Compelling evidence links protein misfolding and its accumulation with neurodegenerative changes. Accordingly, several mechanisms of prion-mediated neurotoxicity have been proposed. In this paper, we provide an overview of the recent knowledge on the mechanisms of neuropathogenesis, the neurotoxic PrP species and the possible therapeutic approaches to treat these devastating disorders.

scholarly journals Prions: Some Details and Diseases

2021 ◽  
Vol 2 (3) ◽  
pp. 80-94
Author(s):  
Saif Jabbar Yasir ◽  
Taghreed Abdul Kareem Al- Makhzoomy
Keyword(s):  
Neurodegenerative Disorders ◽  
Prion Diseases ◽  
Neuronal Loss ◽  
Alpha Synuclein ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Spongiform Encephalopathies ◽  
Incubation Periods ◽  
Jakob Disease

Prion diseases or transmissible spongiform encephalopathies (TSEs) are a family of rare progressive neurodegenerative disorders that affect both humans and animals. They are distinguished by long incubation periods, characteristic spongiform changes associated with neuronal loss, and a failure to induce inflammatory response. Prion diseases in animals, Scrapie in sheep, chronic wasting disease (CWD) in deer, bovine spongiform encephalopathy (commonly known as "mad cow disease") in cattle, and Creutzfeldt-Jakob disease in humans are all examples of infectious diseases. The prion protein (PrP) was identified in a patient in 2015, and it was previously believed to be the cause of all known mammalian prion diseases. However, The protein alpha-synuclein, which is thought to be responsible for MSA, was suggested to be the cause of the disease in 2015.

scholarly journals Classical BSE prions emerge from asymptomatic pigs challenged with atypical/Nor98 scrapie

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Belén Marín ◽  
Alicia Otero ◽  
Séverine Lugan ◽  
Juan Carlos Espinosa ◽  
Alba Marín-Moreno ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Clinical Signs ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Post Inoculation ◽  
Atypical Scrapie ◽  
Wasting Disease ◽  
Spongiform Encephalopathies ◽  
Robust Transmission

AbstractPigs are susceptible to infection with the classical bovine spongiform encephalopathy (C-BSE) agent following experimental inoculation, and PrPSc accumulation was detected in porcine tissues after the inoculation of certain scrapie and chronic wasting disease isolates. However, a robust transmission barrier has been described in this species and, although they were exposed to C-BSE agent in many European countries, no cases of natural transmissible spongiform encephalopathies (TSE) infections have been reported in pigs. Transmission of atypical scrapie to bovinized mice resulted in the emergence of C-BSE prions. Here, we conducted a study to determine if pigs are susceptible to atypical scrapie. To this end, 12, 8–9-month-old minipigs were intracerebrally inoculated with two atypical scrapie sources. Animals were euthanized between 22- and 72-months post inoculation without clinical signs of TSE. All pigs tested negative for PrPSc accumulation by enzyme immunoassay, immunohistochemistry, western blotting and bioassay in porcine PrP mice. Surprisingly, in vitro protein misfolding cyclic amplification demonstrated the presence of C-BSE prions in different brain areas from seven pigs inoculated with both atypical scrapie isolates. Our results suggest that pigs exposed to atypical scrapie prions could become a reservoir for C-BSE and corroborate that C-BSE prions emerge during interspecies passage of atypical scrapie.

Prions: Protein Aggregation and Infectious Diseases

2009 ◽  
Vol 89 (4) ◽  
pp. 1105-1152 ◽  
Author(s):  
Adriano Aguzzi ◽  
Anna Maria Calella
Keyword(s):  
Protein Aggregation ◽  
Prion Diseases ◽  
Physiological Role ◽  
Infectious Agent ◽  
Normal Function ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Pathological Features ◽  
Spongiform Encephalopathies

Transmissible spongiform encephalopathies (TSEs) are inevitably lethal neurodegenerative diseases that affect humans and a large variety of animals. The infectious agent responsible for TSEs is the prion, an abnormally folded and aggregated protein that propagates itself by imposing its conformation onto the cellular prion protein (PrPC) of the host. PrPCis necessary for prion replication and for prion-induced neurodegeneration, yet the proximal causes of neuronal injury and death are still poorly understood. Prion toxicity may arise from the interference with the normal function of PrPC, and therefore, understanding the physiological role of PrPCmay help to clarify the mechanism underlying prion diseases. Here we discuss the evolution of the prion concept and how prion-like mechanisms may apply to other protein aggregation diseases. We describe the clinical and the pathological features of the prion diseases in human and animals, the events occurring during neuroinvasion, and the possible scenarios underlying brain damage. Finally, we discuss potential antiprion therapies and current developments in the realm of prion diagnostics.

scholarly journals Prion Diseases and the Gastrointestinal Tract

2006 ◽  
Vol 20 (1) ◽  
pp. 18-24 ◽  
Author(s):  
Gwynivere A Davies ◽  
Adam R Bryant ◽  
John D Reynolds ◽  
Frank R Jirik ◽  
Keith A Sharkey
Keyword(s):  
Nervous System ◽  
Dendritic Cells ◽  
Enteric Nervous System ◽  
Prion Protein ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Gi Tract ◽  
Spongiform Encephalopathies ◽  
The Brain

The gastrointestinal (GI) tract plays a central role in the pathogenesis of transmissible spongiform encephalopathies. These are human and animal diseases that include bovine spongiform encephalopathy, scrapie and Creutzfeldt-Jakob disease. They are uniformly fatal neurological diseases, which are characterized by ataxia and vacuolation in the central nervous system. Alhough they are known to be caused by the conversion of normal cellular prion protein to its infectious conformational isoform (PrPsc) the process by which this isoform is propagated and transported to the brain remains poorly understood. M cells, dendritic cells and possibly enteroendocrine cells are important in the movement of infectious prions across the GI epithelium. From there, PrPscpropagation requires B lymphocytes, dendritic cells and follicular dendritic cells of Peyer’s patches. The early accumulation of the disease-causing agent in the plexuses of the enteric nervous system supports the contention that the autonomic nervous system is important in disease transmission. This is further supported by the presence of PrPscin the ganglia of the parasympathetic and sympathetic nerves that innervate the GI tract. Additionally, the lymphoreticular system has been implicated as the route of transmission from the gut to the brain. Although normal cellular prion protein is found in the enteric nervous system, its role has not been characterized. Further research is required to understand how the cellular components of the gut wall interact to propagate and transmit infectious prions to develop potential therapies that may prevent the progression of transmissible spongiform encephalopathies.

scholarly journals Toxicological Evaluation of Anti-Scrapie Trimethoxychalcones and Oxadiazoles

2015 ◽  
Vol 87 (2 suppl) ◽  
pp. 1421-1434 ◽  
Author(s):  
CLAUDIA P. FIGUEIREDO ◽  
NATALIA C. FERREIRA ◽  
GISELLE F. PASSOS ◽  
ROBSON DA COSTA ◽  
FERNANDA S. NEVES ◽  
...  
Keyword(s):  
Prion Protein ◽  
Aromatic Compounds ◽  
Prion Diseases ◽  
Intraperitoneal Administration ◽  
Neuroblastoma Cells ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Toxicological Evaluation ◽  
Spongiform Encephalopathies

An altered form of the cellular prion protein, the PrPScor PrPRes, is implicated in the occurrence of the still untreatable transmissible spongiform encephalopathies. We have previously synthesized and characterized aromatic compounds that inhibit protease-resistant prion protein (PrPRes) accumulation in scrapie-infected cells. These compounds belong to different chemical classes, including acylhydrazones, chalcones and oxadiazoles. Some of the active compounds were non-toxic to neuroblastoma cells in culture and seem to possess drugable properties, since they are in agreement with the Lipinski´s rule of 5 and present desirable pharmacokinetic profiles as predicted in silico. Before the evaluation of the in vivo efficacy of the aromatic compounds in scrapie-infected mice, safety assessment in healthy mice is needed. Here we used Swiss mice to evaluate the acute toxicity profile of the six most promising anti-prionic compounds, the 2,4,5-trimethoxychalcones (J1, J8, J20 and J35) and the 1,3,4-oxadiazoles (Y13 and Y17). One single oral administration (300 mg/kg) of J1, J8, J20, J35, Y13 and Y17 or repeated intraperitoneal administration (10 mg/kg, 3 times a week, for 4 weeks) of J1, J8 and J35, did not elicit toxicity in mice. We strongly believe that the investigated trimethoxychalcones and oxadiazoles are interesting compounds to be further analyzed in vivo against prion diseases.

scholarly journals Transmissible spongiform encephalopathy strain, PrP genotype and brain region all affect the degree of glycosylation of PrPSc

2005 ◽  
Vol 86 (1) ◽  
pp. 241-246 ◽  
Author(s):  
Robert A. Somerville ◽  
Scott Hamilton ◽  
Karen Fernie
Keyword(s):  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Infectious Agent ◽  
Host Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Major Influence ◽  
Spongiform Encephalopathy ◽  
Phenotypic Properties ◽  
Spongiform Encephalopathies ◽  
Diagnostic Potential

Transmissible spongiform encephalopathies (TSEs), sometimes known as prion diseases, are caused by an infectious agent whose molecular properties have not been determined. Traditionally, different strains of TSE diseases are characterized by a series of phenotypic properties after passage in experimental animals. More recently it has been recognized that diversity in the degree to which an abnormal form of the host protein PrP, denoted PrPSc, is glycosylated and the migration of aglycosyl forms of PrPSc on immunoblots may have some differential diagnostic potential. It has been recognized that these factors are affected by the strain of TSE agent but also by other factors, e.g. location within the brain. This study shows in some cases, but not others, that host PrP genotype has a major influence on the degree of PrPSc glycosylation and migration on gels and provides further evidence of the effect of brain location. Accordingly both the degree of glycosylation and the apparent molecular mass of PrPSc may be of some value for differential diagnosis between TSE strains, but only when host effects are taken into account. Furthermore, the data inform the debate about how these differences arise, and favour hypotheses proposing that TSE agents affect glycosylation of PrP during its biosynthesis.

Sign in / Sign up

Export Citation Format

Share Document