Expression of cellular prion protein on blood cells: Potential functions in cell physiology and pathophysiology of transmissible spongiform encephalopathy diseases

2001 ◽  
Vol 15 (4) ◽  
pp. 268-281 ◽  
Author(s):  
Jaroslav G. Vostal ◽  
Karel Holada ◽  
Jan Simak
Keyword(s):  
Prion Protein ◽  
Blood Cells ◽  
Transmissible Spongiform Encephalopathy ◽  
Potential Functions ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Cell Physiology

scholarly journals Cellular prion protein status in sheep: tissue-specific biochemical signatures

2001 ◽  
Vol 82 (8) ◽  
pp. 2017-2024 ◽  
Author(s):  
Mohammed Moudjou ◽  
Yveline Frobert ◽  
Jacques Grassi ◽  
Claude La Bonnardière
Keyword(s):  
Skeletal Muscle ◽  
Prion Protein ◽  
Transmissible Spongiform Encephalopathy ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Tissue Specific ◽  
Protein Status ◽  
Low Levels ◽  
Recombinant Prion Protein ◽  
The Brain

Expression of the cellular prion protein PrPC is sine qua none for the development of transmissible spongiform encephalopathy and thus for the accumulation of the illness-associated conformer PrPSc. Therefore, the tissue distribution of PrPC at the protein level in both quantitative and qualitative terms was investigated. PrPC was quantified using a two-site enzyme immunometric assay which was calibrated with purified ovine recombinant prion protein (rPrP). The most PrPC-rich tissue was the brain, followed by the lungs, skeletal muscle, heart, uterus, thymus and tongue, which contained between 20- and 50-fold less PrPC than the brain. The PrPC content of these tissues seems to be comparable between sheep. Other organs, however, showed different, but low, levels of the protein depending on the animal examined. This was also the case for tissues from the gastrointestinal tract. The tissue containing the lowest concentration of PrPC was shown to be the liver, where PrPC was found to be between 564- and 16000-fold less abundant than in the brain. PrPC was concentrated from crude cellular extracts by immunoprecipitation using several monoclonal and polyclonal anti-ovine PrP antibodies. Interestingly, it was observed that the isoform profile of PrPC was tissue-specific. The most atypical electrophoretic profile of PrPC was found in the skeletal muscle, where two polypeptides of 32 and 35 kDa were detected.

Reduction of transmissible spongiform encephalopathy infectivity from human red blood cells with prion protein affinity ligands

Transfusion ◽  
2006 ◽  
Vol 46 (7) ◽  
pp. 1152-1161 ◽  
Author(s):  
Luisa Gregori ◽  
Brian C. Lambert ◽  
Patrick V. Gurgel ◽  
Liliana Gheorghiu ◽  
Peter Edwardson ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Prion Protein ◽  
Blood Cells ◽  
Transmissible Spongiform Encephalopathy ◽  
Spongiform Encephalopathy ◽  
Affinity Ligands ◽  
Human Red Blood Cells ◽  
Protein Affinity

scholarly journals Sheep scrapie susceptibility-linked polymorphisms do not modulate the initial binding of cellular to disease-associated prion protein prior to conversion

2005 ◽  
Vol 86 (9) ◽  
pp. 2627-2634 ◽  
Author(s):  
Alan Rigter ◽  
Alex Bossers
Keyword(s):  
Prion Protein ◽  
Transmissible Spongiform Encephalopathy ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Second Step ◽  
Spongiform Encephalopathy ◽  
Differential Rate ◽  
Allelic Variants ◽  
Scrapie Susceptibility ◽  
Initial Binding

Conversion of the host-encoded protease-sensitive cellular prion protein (PrPC) into the scrapie-associated protease-resistant isoform (PrPSc) of prion protein (PrP) is the central event in transmissible spongiform encephalopathies or prion diseases. Differences in transmissibility and susceptibility are largely determined by polymorphisms in PrP, but the exact molecular mechanism behind PrP conversion and the modulation by disease-associated polymorphisms is still unclear. To assess whether the polymorphisms in either PrPC or PrPSc modulate the initial binding of PrPC to PrPSc, several naturally occurring allelic variants of sheep PrPC and PrPSc that are associated with differential scrapie susceptibility and transmissibility [the phylogenetic wild-type (ARQ), the codon 136Val variant (VRQ) and the codon 171Arg variant (ARR)] were used. Under cell-free PrP conversion conditions known to reproduce the observed in vivo differential scrapie susceptibility, it was found that the relative amounts of PrPC allelic variants bound by various allelic PrPSc variants are PrP-specific and have comparable binding efficiencies. Therefore, the differential rate-limiting step in conversion of sheep PrP variants is not determined by the initial PrPC–PrPSc-binding efficiency, but seems to be an intrinsic property of PrPC itself. Consequently, a second step after PrPC–PrPSc-binding should determine the observed differences in PrP conversion efficiencies. Further study of this second step may provide a future tool to determine the mechanism underlying refolding of PrPC into PrPSc and supports the use of conversion-resistant polymorphic PrPC variants as a potential therapeutic approach to interfere with PrP conversion in transmissible spongiform encephalopathy development.

scholarly journals Identification of Misfolded Proteins in Body Fluids for the Diagnosis of Prion Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Francesca Properzi ◽  
Maurizio Pocchiari
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Clinical Signs ◽  
Meat Products ◽  
Silent Period ◽  
Infectious Agent ◽  
Body Fluids ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy

Transmissible spongiform encephalopathy (TSE) or prion diseases are fatal rare neurodegenerative disorders affecting man and animals and caused by a transmissible infectious agent. TSE diseases are characterized by spongiform brain lesions with neuronal loss and the abnormal deposition in the CNS, and to less extent in other tissues, of an insoluble and protease resistant form of the cellular prion protein (PrPC), namedPrPTSE. In man, TSE diseases affect usually people over 60 years of age with no evident disease-associated risk factors. In some cases, however, TSE diseases are unequivocally linked to infectious episodes related to the use of prion-contaminated medicines, medical devices, or meat products as in the variant Creutzfeldt-Jakob disease (CJD). Clinical signs occur months or years after infection, and during this silent periodPrPTSE, the only reliable marker of infection, is not easily measurable in blood or other accessible tissues or body fluids causing public health concerns. To overcome the limit ofPrPTSEdetection, several highly sensitive assays have been developed, but attempts to apply these techniques to blood of infected hosts have been unsuccessful or not yet validated. An update on the latest advances for the detection of misfolded prion protein in body fluids is provided.

Cellular prion protein is released on exosomes from activated platelets

Blood ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 3907-3911 ◽  
Author(s):  
Catherine Robertson ◽  
Stephanie A. Booth ◽  
Daniel R. Beniac ◽  
Michael B. Coulthart ◽  
Timothy F. Booth ◽  
...  
Keyword(s):  
Prion Protein ◽  
Transmissible Spongiform Encephalopathy ◽  
Cellular Prion Protein ◽  
The Body ◽  
Spongiform Encephalopathy ◽  
Platelet Surface ◽  
Activated Platelets ◽  
Resistant Form ◽  
Granule Membrane ◽  
Physiologic Function

Cellular prion protein (PrPC) is a glycophosphatidylinositol (GPI)–anchored protein, of unknown function, found in a number of tissues throughout the body, including several blood components of which platelets constitute the largest reservoir in humans. It is widely believed that a misfolded, protease-resistant form of PrPC, PrPSc, is responsible for the transmissible spongiform encephalopathy (TSE) group of fatal neurodegenerative diseases. Although the pathogenesis of TSEs is poorly understood, it is known that PrPC must be present in order for the disease to progress; thus, it is important to determine the physiologic function of PrPC. Resolving the location of PrPC in blood will provide valuable clues as to its function. PrPC was previously shown to be on the alpha granule membrane of resting platelets. In the current study platelet activation led to the transient expression of PrPC on the platelet surface and its subsequent release on both microvesicles and exosomes. The presence of PrPC on platelet-derived exosomes suggests a possible mechanism for PrPC transport in blood and for cell-to-cell transmission.

scholarly journals Classical and Atypical Scrapie in Sheep and Goats. Review on the Etiology, Genetic Factors, Pathogenesis, Diagnosis, and Control Measures of Both Diseases

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 691
Author(s):  
Cristina Acín ◽  
Rosa Bolea ◽  
Marta Monzón ◽  
Eva Monleón ◽  
Bernardino Moreno ◽  
...  
Keyword(s):  
Prion Protein ◽  
Genetic Factors ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Fatal Outcome ◽  
Small Ruminants ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Atypical Scrapie ◽  
Sheep And Goats

Prion diseases, such as scrapie, are neurodegenerative diseases with a fatal outcome, caused by a conformational change of the cellular prion protein (PrPC), originating with the pathogenic form (PrPSc). Classical scrapie in small ruminants is the paradigm of prion diseases, as it was the first transmissible spongiform encephalopathy (TSE) described and is the most studied. It is necessary to understand the etiological properties, the relevance of the transmission pathways, the infectivity of the tissues, and how we can improve the detection of the prion protein to encourage detection of the disease. The aim of this review is to perform an overview of classical and atypical scrapie disease in sheep and goats, detailing those special issues of the disease, such as genetic factors, diagnostic procedures, and surveillance approaches carried out in the European Union with the objective of controlling the dissemination of scrapie disease.

scholarly journals PAD-Beads enrichment enhances detection of PrPSc using real-time quaking-induced conversion

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Soyoun Hwang ◽  
Rohana P. Dassanayake ◽  
Eric M. Nicholson
Keyword(s):  
Real Time ◽  
Prion Protein ◽  
Magnetic Beads ◽  
Transmissible Spongiform Encephalopathy ◽  
Biological Tissues ◽  
Cellular Prion Protein ◽  
Detection Sensitivity ◽  
Spongiform Encephalopathy ◽  
Lymphoid Tissues

Abstract Objective Scrapie is a transmissible spongiform encephalopathy (TSE) that naturally occurs in sheep and goats. This fatal neurodegenerative disease results from misfolding of the normal cellular prion protein (PrPC) to a pathogenic prion protein form (PrPSc). This pathogenic form, PrPSc, accumulates in the brain and lymphoid tissues. The presence of PrPSc can be detected by an in vitro conversion assay known as real-time quaking induced conversion (RT-QuIC). RT-QuIC has been used to detect PrPSc in a variety of biological tissues from brains to fluids. While this technique is both rapid and sensitive, enhancing the detection of prions would be valuable in the diagnostic laboratories. Results In this study, we assessed whether PrPSc detection sensitivity of RT-QuIC can be increased by enriching PrPSc in scrapie tissue homogenates using commercially available aggregated protein binding ligands coated magnetic beads (PAD-Beads). Coupling of RT-QuIC to PAD-Beads based cleanup allowed detection of PrPSc rapidly and without dilution of scrapie sheep brain homogenates prior to RT-QuIC. The PAD-Beads sample pretreatment step prior to RT-QuIC is a useful enhancement in the diagnosis of TSEs.

MOLECULAR DYNAMIC SIMULATION OF V176G MUTATION ASSOCIATED WITH GERSTMANN–STRÄUSSLER–SCHEINKER AT ELEVATED TEMPERATURE

2016 ◽  
Vol 78 (2) ◽  
Author(s):  
Ashraf Fadhil Jomah ◽  
Mohd Shahir Shamsir
Keyword(s):  
Hydrogen Bonds ◽  
Prion Protein ◽  
Novel Mutation ◽  
Solvent Accessibility ◽  
Transmissible Spongiform Encephalopathy ◽  
Salt Bridge ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Α Helix ◽  
Dynamics Simulations

The transformation of cellular prion protein (PrPc) into pathogenic conformer (PrPSc) in transmissible spongiform encephalopathy is expedited by mutations in the prion protein. One recently reported novel mutation V176G is located in region of the protein known to cause Creutzfeldt-Jakob disease (CJD) but possess a unique neuropathological profile and spongiform alteration similar to Gerstmann–Sträussler–Scheinker syndrome (GSS). Using molecular dynamics simulations; the denaturation of the prion structure with V176G at 500K was studied to identify the dynamics in structural properties such as salt bridge, solvent accessibility, hydrogen bonds and hydrophobicity. The simulations revealed that the heat-induced unfolding caused destabilization of the native structure of PrP and affecting the β-sheet region of the structure more than the α-helix. Unique salt bridge formation suggests conformational orientation that may be attributed to the V176G mutation. The mutation effects showed an increased fluctuation of the H1 region, gain of hydrogen bonds between H3 and H2 which may be part of the oligomerization pathway and determine the features of the PrPSc assemblies.

scholarly journals Prion Protein Signaling in the Nervous System—A Review and Perspective

2014 ◽  
Vol 3 ◽  
pp. STI.S12319 ◽  
Author(s):  
Ann Liebert ◽  
Brian Bicknell ◽  
Roger Adams
Keyword(s):  
Nervous System ◽  
Prion Protein ◽  
Transmissible Spongiform Encephalopathy ◽  
Redox Status ◽  
Scaffolding Protein ◽  
Spongiform Encephalopathy ◽  
Cell Physiology ◽  
Protein Signaling ◽  
Neural Transmission ◽  
Multiple Ligands

Prion protein (PrPC) was originally known as the causative agent of transmissible spongiform encephalopathy (TSE) but with recent research, its true function in cells is becoming clearer. It is known to act as a scaffolding protein, binding multiple ligands at the cell membrane and to be involved in signal transduction, passing information from the extracellular matrix (ECM) to the cytoplasm. Its role in the coordination of transmitters at the synapse, glyapse, and gap junction and in short- and long-range neurotrophic signaling gives PrPC a major part in neural transmission and nervous system signaling. It acts to regulate cellular function in multiple targets through its role as a controller of redox status and calcium ion flux. Given the importance of PrPC in cell physiology, this review considers its potential role in disease apart from TSE. The putative functions of PrPC point to involvement in neurodegenerative disease, neuropathic pain, chronic headache, and inflammatory disease including neuroinflammatory disease of the nervous system. Potential targets for the treatment of disease influenced by PrPC are discussed.

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