PrPSc Proteins: Abnormal isoform of prion proteins (PRIONS) resulting from a posttranslational modification of the cellular prion protein (PRPC PROTEINS). PrPSc are disease-specific proteins seen in certain human and animal neurodegenerative diseases (PRION DISEASES).Prion Diseases: A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83)Prions: Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL.PrPC Proteins: Normal cellular isoform of prion proteins (PRIONS) encoded by a chromosomal gene and found in normal and scrapie-infected brain tissue, and other normal tissue. PrPC are protease-sensitive proteins whose function is unknown. Posttranslational modification of PrPC into PrPSC leads to infectivity.Creutzfeldt-Jakob Syndrome: A rare transmissible encephalopathy most prevalent between the ages of 50 and 70 years. Affected individuals may present with sleep disturbances, personality changes, ATAXIA; APHASIA, visual loss, weakness, muscle atrophy, MYOCLONUS, progressive dementia, and death within one year of disease onset. A familial form exhibiting autosomal dominant inheritance and a new variant CJD (potentially associated with ENCEPHALOPATHY, BOVINE SPONGIFORM) have been described. Pathological features include prominent cerebellar and cerebral cortical spongiform degeneration and the presence of PRIONS. (From N Engl J Med, 1998 Dec 31;339(27))Gerstmann-Straussler-Scheinker Disease: An autosomal dominant familial prion disease with a wide spectrum of clinical presentations including ATAXIA, spastic paraparesis, extrapyramidal signs, and DEMENTIA. Clinical onset is in the third to sixth decade of life and the mean duration of illness prior to death is five years. Several kindreds with variable clinical and pathologic features have been described. Pathologic features include cerebral prion protein amyloidosis, and spongiform or neurofibrillary degeneration. (From Brain Pathol 1998 Jul;8(3):499-513; Brain Pathol 1995 Jan;5(1):61-75)Endopeptidase K: An enzyme that catalyzes the hydrolysis of keratin, and of other proteins with subtilisin-like specificity. It hydrolyses peptide amides. Endopeptidase K is from the mold Tritirachium album Limber. (Enzyme Nomenclature, 1992) EC 3.4.21.64.Insomnia, Fatal Familial: An autosomal dominant disorder characterized by degeneration of the THALAMUS and progressive insomnia. It is caused by a mutation in the prion protein (PRIONS).Scrapie: A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called PRIONS.Encephalopathy, Bovine Spongiform: A transmissible spongiform encephalopathy of cattle associated with abnormal prion proteins in the brain. Affected animals develop excitability and salivation followed by ATAXIA. This disorder has been associated with consumption of SCRAPIE infected ruminant derived protein. This condition may be transmitted to humans, where it is referred to as variant or new variant CREUTZFELDT-JAKOB SYNDROME. (Vet Rec 1998 Jul 25;143(41):101-5)Amyloid: A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.Kuru: A prion disease found exclusively among the Fore linguistic group natives of the highlands of NEW GUINEA. The illness is primarily restricted to adult females and children of both sexes. It is marked by the subacute onset of tremor and ataxia followed by motor weakness and incontinence. Death occurs within 3-6 months of disease onset. The condition is associated with ritual cannibalism, and has become rare since this practice has been discontinued. Pathologic features include a noninflammatory loss of neurons that is most prominent in the cerebellum, glial proliferation, and amyloid plaques. (From Adams et al., Principles of Neurology, 6th ed, p773)Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Wasting Disease, Chronic: A transmissible spongiform encephalopathy (prion disease) of DEER and elk characterized by chronic weight loss leading to death. It is thought to spread by direct contact between animals or through environmental contamination with the prion protein (PRIONS).Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Nuclear Magnetic Resonance, Biomolecular: NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Infectious Disease Incubation Period: The amount time between exposure to an infectious agent and becoming symptomatic.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Circular Dichroism: A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Deer: The family Cervidae of 17 genera and 45 species occurring nearly throughout North America, South America, and Eurasia, on most associated continental islands, and in northern Africa. Wild populations of deer have been established through introduction by people in Cuba, New Guinea, Australia, New Zealand, and other places where the family does not naturally occur. They are slim, long-legged and best characterized by the presence of antlers. Their habitat is forests, swamps, brush country, deserts, and arctic tundra. They are usually good swimmers; some migrate seasonally. (Walker's Mammals of the World, 5th ed, p1362)Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Mesocricetus: A genus of the family Muridae having three species. The present domesticated strains were developed from individuals brought from Syria. They are widely used in biomedical research.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.PrP 27-30 Protein: Protease-resistant core of PrPSC, the abnormal isoform of prion proteins (PRIONS). PrP 27-30 is produced by limited proteolysis of the N-terminus of PrPSc.Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Copper: A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.Methionine: A sulfur-containing essential L-amino acid that is important in many body functions.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Mice, Inbred C57BLNeurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Glycosylphosphatidylinositols: Compounds containing carbohydrate or glycosyl groups linked to phosphatidylinositols. They anchor GPI-LINKED PROTEINS or polysaccharides to cell membranes.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.Dendritic Cells, Follicular: Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional DENDRITIC CELLS associated with T-CELLS. They are derived from MESENCHYMAL STEM CELLS and are negative for class II MHC antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have FC RECEPTORS and C3B RECEPTORS that hold antigen in the form of ANTIGEN-ANTIBODY COMPLEXES on their surfaces for long periods for recognition by B-CELLS.Proteostasis Deficiencies: Disorders caused by imbalances in the protein homeostasis network - synthesis, folding, and transport of proteins; post-translational modifications; and degradation or clearance of misfolded proteins.Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Repetitive Sequences, Amino Acid: A sequential pattern of amino acids occurring more than once in the same protein sequence.Quinacrine: An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.Ruminants: A suborder of the order ARTIODACTYLA whose members have the distinguishing feature of a four-chambered stomach, including the capacious RUMEN. Horns or antlers are usually present, at least in males.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Pentosan Sulfuric Polyester: A sulfated pentosyl polysaccharide with heparin-like properties.Bentonite: A colloidal, hydrated aluminum silicate that swells 12 times its dry size when added to water.Amyloidogenic Proteins: Proteins that form the core of amyloid fibrils. For example, the core of amyloid A is formed from amyloid A protein, also known as serum amyloid A protein or SAA protein.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Neuroblastoma: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)GPI-Linked Proteins: A subclass of lipid-linked proteins that contain a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE which holds them to the CELL MEMBRANE.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Kinetics: The rate dynamics in chemical or physical systems.Libya: A country in northern Africa, bordering the Mediterranean Sea, between Egypt, Tunisia, and Algeria, having southern border with Chad, Niger, and Sudan. Its capital is Tripoli.Protein Denaturation: Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Gene Expression Regulation, Plant: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Plants, Genetically Modified: PLANTS, or their progeny, whose GENOME has been altered by GENETIC ENGINEERING.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Cell Line, Tumor: A cell line derived from cultured tumor cells.Nerve Degeneration: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties.Goats: Any of numerous agile, hollow-horned RUMINANTS of the genus Capra, in the family Bovidae, closely related to the SHEEP.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).

*Giovanna Mallucci

Previously, the team found that the accumulation of misfolded proteins in mice with prion disease over-activates a natural ... You don't know what's going to work in humans but it means we don't have to wait 20 years to find something." She added: "We ... Toxicology Unit in Leicester originally discovered that this accumulation of misfolded proteins in mice with prion disease over ... Misfolded proteins build up in the brain in several neurodegenerative diseases and are a major factor in dementias such as ...

*Nerve tissue protein

Neurodegenerative disease is caused by prions accumulation of PrPsc. The brains of humans or animals affected with prion ... Neuronal Apoptosis-Inhibitory Protein Neuronal Calcium-Sensor Proteins Neuropeptides Olfactory Marker Protein S100 Proteins ... Prion protein triggers are an important factor in the signals that ensure myelin maintenance and are distinct from those that ... Prion protein and antibodies POM1 and POM3, which recognize epitopes in the terminus (around amino acids (aa) 140-152) and ...

*PRNP

... (prion protein) is the human gene encoding for the major prion protein PrP (proetase-resistant-protein, Pr for prion, and ... Laurén J (2014). "Cellular prion protein as a therapeutic target in Alzheimer's disease". Journal of Alzheimer's Disease. 38 (2 ... Accumulation of PrPSc corresponds with progression of neurodegeneration and is the proposed cause. Some PRNP mutations lead to ... a prion disease with a mutation at codon 178 of the prion protein gene". N. Engl. J. Med. 326 (7): 444-9. doi:10.1056/ ...

*Protein folding

Aggregated proteins are associated with prion-related illnesses such as Creutzfeldt-Jakob disease, bovine spongiform ... Chiti F, Dobson CM (2006). "Protein misfolding, functional amyloid, and human disease". Annual Review of Biochemistry. 75: 333- ... The misfolding of proteins can trigger the further misfolding and accumulation of other proteins into aggregates or oligomers. ... FoldIt - Folding Protein Game [email protected] [email protected] Human Proteome Folding Project BHAGEERATH-H: Protein tertiary structure ...

*Molecular neuroscience

It is also possible that a receptor for amyloid-β oligomers could be a prion protein. Parkinson's disease is the second most ... in the brain is integral in the incidence of Alzheimer's disease. Accumulation is purported to block hippocampal long-term ... "Epigenetics and the Human Brain". Genetics Science and Learning Center at The University of Utah. Retrieved 10 November 2013. ... Examples of diseases with sex biases in development include Huntington's disease, cerebral ischemia, and Alzheimer's disease. ...

*PRNP

... (PRioN Protein) is the human gene encoding for the major prion protein PrP (for prion protein), also known as CD230 ( ... Zhou J, Liu B (May 2013). "Alzheimer's disease and prion protein". Intractable & Rare Diseases Research. 2 (2): 35-44. doi: ... Accumulation of PrPSc corresponds with progression of neurodegeneration and is the proposed cause. Some PRNP mutations lead to ... Laurén J (2014). "Cellular prion protein as a therapeutic target in Alzheimer's disease". Journal of Alzheimer's Disease. 38 (2 ...

*Neurodegeneration

prion: main component of prion diseases and transmissible spongiform encephalopathies.. Intracellular mechanisms[edit]. Protein ... Alzheimer's disease has been hypothesized to be a protein misfolding disease (proteopathy), caused by accumulation of ... Most relevant human neurodegenerative diseases share the property of having abnormal structures made up of proteins and ... Parkinson's disease and Huntington's disease are both late-onset and associated with the accumulation of intracellular toxic ...

*Bovine spongiform encephalopathy

"Human Prion Protein Gene: Two Different 24 BP Deletions in an Atypical Alzheimer's Disease Family". American Journal of Medical ... Immunohistochemistry can be used to demonstrate prion protein accumulation. In 2010, a team from New York described detection ... The infectious agent in BSE is a specific type of misfolded protein called a prion. Prions can be transmitted to humans by ... "Organ distribution of prion proteins in variant Creutzfeldt-Jakob disease". The Lancet Infectious Diseases. 3 (4): 214-222. doi ...

*Prion

Accumulation of the abnormally folded PrPSc form of the PrP protein is a characteristic of the disease, but it is present at ... The human prion disease variant Creutzfeldt-Jakob disease, however, is believed to be caused by a prion that typically infects ... Prion protein - PrP, inherited prion disease and transgenic animal models. The Surprising World of Prion Biology-A New ... "mad cow disease". Human prion diseases include Creutzfeldt-Jakob disease (CJD) and its variant (vCJD), Gerstmann-Sträussler- ...

*Neuroscience of aging

... in a similar mechanism to the prion propagation of Creutzfeldt-Jakob disease. Similarly the protein alpha-synuclein is ... For example, the tau hypothesis to Alzheimer's proposes that tau protein accumulation results in the breakdown neuron ... PMC 2596698 . Reuter-Lorenz, Patricia A.; Park, Denise C. (8 January 2017). "Human Neuroscience and the Aging Mind: A New Look ... Diseases commonly associated with old age include Multiple System Atrophy Parkinson's Disease Alzheimer's Disease Stroke. ...

*Posterior cingulate

It has been found that neurodegenerative diseases spread 'prion-like' through the brain. For example, when the proteins amyloid ... While many of the connections in non-human primates may be present in humans, they are less well documented. Studies have shown ... Therefore, the functional abnormalities of the PCC might be an accumulation of remote and widespread damage in the brain. The ... A Human fMRI Study". Frontiers in Human Neuroscience. 11. doi:10.3389/fnhum.2017.00647. ISSN 1662-5161. Posterior cingulate in ...

*Microglia

... l degeneration and death have been reported in research on Prion disease, Schizophrenia and Alzheimer's disease, ... Another factor might be the accumulation of advanced glycation endproducts, which accumulate with aging. These proteins are ... Interestingly, the downregulation of Cx3cr1 in humans without Rett syndrome is associated with symptoms similar to ... such as Alzheimer's disease, Parkinson's disease, Multiple sclerosis, as well as cardiac diseases, glaucoma, and viral and ...

*Mechanistic target of rapamycin

"mTOR protein interactors". Human Protein Reference Database. Johns Hopkins University and the Institute of Bioinformatics. ... mediates cell death in prion diseases through sustained translational inhibition. Some evidence points to mTOR's role in ... discovery represents a potential novel therapeutic approach for glycogen storage diseases that involve glycogen accumulation in ... several age-associated diseases including neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. ...

*Posterior cingulate cortex

It has been found that neurodegenerative diseases spread 'prion-like' through the brain.[4] For example, when the proteins ... Human structure[edit]. While many of the connections in non-human primates may be present in humans, they are less well ... Therefore, functional abnormalities of the PCC might be an accumulation of remote and widespread damage in the brain.[4] ... Alzheimer's disease[edit]. The PCC is commonly affected by neurodegenerative disease.[15] In fact, reduced metabolism in the ...

*Dentatorubral-pallidoluysian atrophy

... mice express full-length human atrophin-1 with 65 CAG repeats under transcriptional control of the mouse prion protein promoter ... Like in human brains, nuclear accumulation was demonstrated and occasional NIIs were visualised, but the NIIs did not stain for ... 1999). "Transgenic mice harboring a full-length human DRPLA gene with highly expanded CAG repeats exhibit severe disease ... While the role of NIIs (pathologic or protective) is unclear, the diffuse accumulation of mutant protein is regarded as toxic. ...

*Gene expression

Several neurodegenerative and other diseases are believed to result from the accumulation of misfolded proteins. Many allergies ... Hebert DN, Molinari M (October 2007). "In and out of the ER: protein folding, quality control, degradation, and related human ... Failure to fold into the intended shape usually produces inactive proteins with different properties including toxic prions. ... Once protein synthesis is complete, the level of expression of that protein can be reduced by protein degradation. There are ...

*Creutzfeldt-Jakob disease

Gill, Noel (2013). "Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: ... as a study by the Health Protection Agency show around 1 in 2000 people in the UK shows signs of abnormal prion accumulation. ... "Neuropathological diagnosis of human prion disease; morphological studies". In H. F. Baker; R. M. Ridley. Prion Diseases. pp. ... Transmissible spongiform encephalopathy diseases are caused by prions. Prions are proteins that occur normally in neurons of ...

*Epigenetics

Prions[edit]. For more details on this topic, see Fungal prions.. Prions are infectious forms of proteins. In general, proteins ... human development, and the origins of cancer, heart disease, mental illness, as well as several other conditions. Some ... This accumulation, in turn, directs recruitment and activation of the chromatin remodeling protein ALC1 that can cause ... Prions can have a phenotypic effect through the sequestration of protein in aggregates, thereby reducing that protein's ...

*Epigenetics

Prions are infectious forms of proteins. In general, proteins fold into discrete units that perform distinct cellular functions ... human development, and the origins of cancer, heart disease, mental illness, as well as several other conditions. Some ... This accumulation, in turn, directs recruitment and activation of the chromatin remodeling protein ALC1 that can cause ... Prions can have a phenotypic effect through the sequestration of protein in aggregates, thereby reducing that protein's ...

*Evolvability

Many human diseases are not static phenomena, but capable of evolution. Viruses, bacteria, fungi and cancers evolve to be ... Firstly, for protein engineering it is important to understand the factors that determine how much a protein function can be ... The yeast prion [PSI+] may also be an example of the evolution of evolvability through evolutionary capacitance. An ... Temporary robustness, or canalisation, may lead to the accumulation of significant quantities of cryptic genetic variation. In ...

*Proteopathy

... or protein misfolding diseases) include such diseases as Creutzfeldt-Jakob disease and other prion diseases, Alzheimer's ... Eisenberg, D; Jucker, M (2012). "The amyloid state of proteins in human diseases". Cell. 148: 1188-1203. doi:10.1016/j.cell. ... Spinner NB (2000). "CADASIL: Notch signaling defect or protein accumulation problem?". J Clin Invest. 105 (5): 561-562. doi: ... protein]; -pathy [suff. disease]; proteopathies pl.; proteopathic adj.) refers to a class of diseases in which certain proteins ...

*Biochemistry of Alzheimer's disease

Alzheimer's disease has been identified as a protein misfolding disease, or proteopathy, due to the accumulation of abnormally ... Although AD shares pathophysiological mechanisms with prion diseases, it is not transmissible like prion diseases. Amyloid-beta ... Large human genes are highly enriched in cell adhesion Gene Ontology (GO) terms and many of them map to chromosomal fragile ... AD has been identified as a protein misfolding disease due to the accumulation of abnormally folded amyloid beta protein in the ...

*Endoplasmic reticulum

"Oral Treatment Targeting the Unfolded Protein Response Prevents Neurodegeneration and Clinical Disease in Prion-Infected Mice ... The UPR is activated in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum ... "XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease". Cell. 134 (5): ... Sustained overactivation of the UPR has been implicated in prion diseases as well as several other neurodegenerative diseases ...

*Amyloid beta

The other protein implicated in Alzheimer's disease, tau protein, also forms such prion-like misfolded oligomers, and there is ... To date, human testing has been avoided due to concern that it might interfere with signaling via Notch proteins and other cell ... Adults with Down syndrome had accumulation of amyloid in association with evidence of Alzheimer's disease, including declines ... a protein fold shared by other peptides such as the prions associated with protein misfolding diseases. Recent research ...

*Symphogen

Development of recombinant human polyclonal antibodies for the treatment of complex human diseases" Expert Opinion on ... Due to the efficiency of Sym004 induction of receptor internalization, repeat dose studies showed little accumulation of Sym004 ... Symphogen is a biotechnology company located in Copenhagen, Denmark that develops protein drugs based on recombinant monoclonal ... these antibodies are produced with no risk of viral or prion transmission according to Symphogen. This new class of therapeutic ...
Human prion diseases are fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease, fatal familial insomnia, kuru and variant CJD (vCJD; Collinge 2001, 2005; Wadsworth & Collinge 2007). Their central feature is the post-translational conversion of host-encoded, cellular prion protein (PrPC) to an abnormal isoform, designated PrPSc (Prusiner 1982; Collinge 2001). Substantial evidence indicates that an abnormal PrP isoform is the principal, if not the sole, component of the transmissible infectious agent, or prion (Prusiner 1982; Collinge 2001; Weissmann 2004; Collinge & Clarke 2007). Human prion diseases are biologically unique in that the disease process can be triggered through inherited germ line mutations in the ...
It is sometimes forgotten that in the story of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease there is but one incontestable fact, that bovine spongiform encephalopathy is the cause of variant Creutzfeldt-Jakob disease. First suggested by their temporospatial association and the distinctive features of variant Creutzfeldt-Jakob disease, the link has since been proved by their equally distinctive and shared biological and molecular features.1-3 All the rest is speculation, more or less plausible according to the arguments advanced and the absence of any satisfactory alternative explanations.. From an epidemiological point of view bovine spongiform encephalopathy has been a classic epidemic and will undoubtedly become a textbook example for students (fig 1). From economic, political, and medical points of view it has been an unmitigated disaster. Why did it begin when it did, and how did it happen? ...
The agent that causes bovine spongiform encephalopathy (BSE) may be infecting small ruminants, which could have serious implications for human health. To distinguish BSE from scrapie and to examine the molecular characteristics of the protease-resistant prion protein (PrP(res)), we used a specifically designed Western blot method to test isolates from 648 sheep and 53 goats. During 2002-2009, classical non-Nor98 transmissible spongiform encephalopathy had been confirmed among ≈1.7 million small ruminants in France. Five sheep and 2 goats that showed a PrP(res) pattern consistent with BSE, or with the CH1641 experimental scrapie source, were identified. Later, bioassays confirmed infection by the BSE agent in 1 of the 2 goats. Western blot testing of the 6 other isolates showed an additional C-terminally cleaved PrP(res) product, with an unglycosylated band at ≈14 kDa, similar to that found in the CH1641 experimental scrapie isolate and ...
Author Summary The transmissible agent of prion disease consists of a prion protein in its abnormal conformation (PrPSc), which replicates itself according to the template-assisted mechanism. This mechanism postulates that the folding pattern of a newly recruited polypeptide chain accurately reproduces that of a PrPSc. The current study reports that infectious prions and transmissible prion disease can be triggered in wild type animals by amyloid fibrils produced from recombinant prion prtotein, which are structurally different from PrPSc and lacks any detectable PrPSc particles. This work introduces a new hypothesis that transmissible prion diseases can be induced by prion protein structures different from that of authentic ...
Transmissible spongiform encephalopathies are characterized by the accumulation of PrPSc, a protease-resistant form of a host-derived protein termed PrPC. Substantial evidence indicates that PrPSc represents an essential component of the infectious agent, which is termed prion. The accumulation of PrPSc within the central nervous system of prion-infected organisms is a dynamic process that is regulated both by production and by clearance of PrPSc. Although several proteases have been implicated in proteolysis of PrPC, the mechanisms underlying proteolysis of PrPSc remain unclear. Here, it was investigated whether neprilysin, a metalloprotease known to degrade extracellular amyloidogenic proteins such as amyloid-β, plays a role in prion pathogenesis in vivo. As neprilysin has a broad substrate specificity and is localized subcellularly in the ...
The study results, reported by NIH scientists at the National Institute of Allergy and Infectious Diseases (NIAID), are similar to findings from two newly reported human cases of the prion disease Gerstmann-Straussler-Scheinker syndrome (GSS). This finding represents a new mechanism of prion disease brain damage, according to study author Bruce Chesebro, M.D., chief of the Laboratory of Persistent Viral Diseases at NIAIDs Rocky Mountain Laboratories.. Prion diseases, also known as transmissible spongiform encephalopathies, primarily damage the brain. Prion diseases include mad cow disease or bovine spongiform encephalopathy in cattle; scrapie in sheep; sporadic Creutzfeldt-Jakob disease (CJD), variant CJD and GSS in humans; and chronic wasting disease in deer, elk and ...
The risks posed to human health by individual animal prion diseases cannot be determined a priori and are difficult to address empirically. The fundamental event in prion disease pathogenesis is thought to be the seeded conversion of normal prion protein to its pathologic isoform. We used a rapid molecular conversion assay (protein misfolding cyclic amplification) to test whether brain homogenates from specimens of classical bovine spongiform encephalopathy (BSE), atypical BSE (H-type BSE and L-type BSE), classical scrapie, atypical scrapie, and chronic wasting disease can convert normal human prion protein to the abnormal disease-associated form. None of the tested prion isolates from diseased animals were as efficient as classical BSE in ...
Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that include Creutzfeldt-Jakob disease, bovine spongiform encephalopathy and sheep scrapie. TSE disease pathology and mechanisms within the central nervous system (CNS) of an infected host largely remains unclear. At the cellular level, the uptake of protease resistant prion protein (PrP-res), which strongly correlates with infectivity and is a valid marker for TSE infection, is one of the earliest events that must occur during TSE infection. Given the difficulty of clearly distinguishing input PrP-res from either PrP-res or protease-sensitive PrP (PrP-sen) made by the cell, the uptake of PrP-res from an infectious inoculum into the host cell remains a poorly understood process. Through the development of a novel assay to exclusively detect input PrP-res we hypothesized that the acute infection of cells by PrP-res is mediated through general processes such ...
Background. Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases caused by novel infectious agents referred to as prions. Prions appear to be composed primarily, if not exclusively, of a misfolded isoform of the cellular prion protein. TSE infectivity is remarkably stable and can resist many aggressive decontamination procedures, increasing human, livestock and wildlife exposure to TSEs. Findings. We tested the hypothesis that UV-ozone treatment reduces levels of the pathogenic prion protein and inactivates the infectious agent. We found that UV-ozone treatment decreased the carbon and prion protein content in infected brain homogenate to levels undetectable by dry-ashing carbon analysis or immunoblotting, ...
Define transmissible neurodegenerative disease. transmissible neurodegenerative disease synonyms, transmissible neurodegenerative disease pronunciation, transmissible neurodegenerative disease translation, English dictionary definition of transmissible neurodegenerative disease. n. 1. An abnormal condition of a part, organ, or system of an organism resulting from various causes, such as infection, inflammation, environmental...
Prion protein (PrP) is a membrane glycosylphosphatidylinositol (GPI)-anchored glycoprotein that is encoded by the PRNP gene and is highly conserved among mammals. PrP contains an unstable region consisting of five octapeptide repeats; mutations in this region are associated with Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Gerstmann-Straussler disease, Huntington disease-like 1, and kuru (a type of transmissible spongiform encephalopathy, TSE). The function of PrP is not clear, although it is known to bind copper ions. PrP exists as a normal cellular isoform (PrPC) that can undergo refolding to a conformational isoform known as scrapie isoform (PrPSc). PrPSc forms compact aggregates that are highly resistant to proteolysis. The conversion of PrPC to PrPSc is postulated to be the mechanism involved in transmission of TSEs. PrP is also known as prion protein (p27-30); major ...
Prion protein (PrP) is a membrane glycosylphosphatidylinositol (GPI)-anchored glycoprotein that is encoded by the PRNP gene and is highly conserved among mammals. PrP contains an unstable region consisting of five octapeptide repeats; mutations in this region are associated with Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Gerstmann-Straussler disease, Huntington disease-like 1, and kuru (a type of transmissible spongiform encephalopathy, TSE). The function of PrP is not clear, although it is known to bind copper ions. PrP exists as a normal cellular isoform (PrPC) that can undergo refolding to a conformational isoform known as scrapie isoform (PrPSc). PrPSc forms compact aggregates that are highly resistant to proteolysis. The conversion of PrPC to PrPSc is postulated to be the mechanism involved in transmission of TSEs. PrP is also known as prion protein (p27-30); major ...
Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE) during the bovine spongiform encephalopathy (BSE) epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD) remains an open question. Variation in the host-encoded prion protein (PrPC) largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrPC protein from 609 animal samples comprising 29 species from 22 genera ...
Interpretive Summary: The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed ...
The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is caused by a prion strain whose biological properties differ from those of typical BSE, resulting in a clinically and pathologically distinct phenotype. Whether peripheral tissues of BASE-affected cattle contain infectivity is unknown. This is a critical issue since the BASE prion is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible. We carried out bioassays in transgenic mice overexpressing bovine PrP (Tgbov XV) and found infectivity in a variety of skeletal muscles from cattle with natural and experimental BASE. Noteworthy, all BASE muscles used for inoculation transmitted disease, although the attack rate differed between experimental and natural cases (~70% versus ~10%, respectively). This difference was likely related to different prion titers, possibly ...
PRIO_HUMAN] Note=PrP is found in high quantity in the brain of humans and animals infected with neurodegenerative diseases known as transmissible spongiform encephalopathies or prion diseases, like: Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI), Gerstmann-Straussler disease (GSD), Huntington disease-like type 1 (HDL1) and kuru in humans; scrapie in sheep and goat; bovine spongiform encephalopathy (BSE) in cattle; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of mule deer and elk; feline spongiform encephalopathy (FSE) in cats and exotic ungulate encephalopathy (EUE) in nyala and greater kudu. The prion diseases illustrate three manifestations of CNS degeneration: (1) infectious (2) sporadic and (3) dominantly inherited forms. TME, CWD, BSE, FSE, EUE are all thought to occur after consumption of ...
CiteSeerX - Document Details (Isaac Councill, Lee Giles, Pradeep Teregowda): Prion diseases, or transmissible spongiform encephalopathies (TSE), are a group of neurodegenerative disorders affecting both humans and animals. Prion diseases are unique in that they can be inherited, can occur sporadically, or be infectious. Stanley Prusiner introduced the term prion- (proteinaceous infectious particle) and proposed that the infectious agent in prion diseases is composed mainly or entirely of an abnormal conformation of an otherwise normal host-encoded glycoprotein called the prion protein (PrP)1. This hypothesis was initially greeted with great skepticism in the scientific community but then later was widely acknowledged to be ...
Chronic wasting disease (CWD) is one of three naturally occurring forms of prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie in sheep. CWD is contagious and affects captive as well as free ranging cervids. As long as there is no definite answer of whether CWD can breach the species barrier to humans precautionary measures especially for the protection of consumers need to be considered. In principle, different strains of CWD may be associated with different risks of transmission to humans. Sophisticated strain differentiation as accomplished for other prion diseases has not yet been established for CWD. However, several different findings indicate that there exists more than one strain of CWD agent in cervids. We have analysed a set of CWD isolates from white-tailed deer and could detect at least two biochemically different forms of ...
HOUSTON - The brain damage that characterizes Alzheimers disease may originate in a form similar to that of infectious prion diseases such as bovine spongiform encephalopathy (mad cow) and Creutzfeldt-Jakob, according to newly published research by The University of Texas Health Science Center at Houston (UTHealth). "Our findings open the possibility that some of the sporadic Alzheimers cases may arise from an infectious process, which occurs with other neurological diseases such as mad cow and its human form, Creutzfeldt-Jakob disease," said Claudio Soto, Ph.D., professor of neurology at The University of Texas Medical School at Houston, part of UTHealth. "The underlying mechanism of Alzheimers disease is very similar to the prion diseases. It involves a normal protein that becomes misshapen and is able to spread by transforming good ...
TUESDAY, JULY 18, 2017 MINK FARMING USA TRANSMISSIBLE MINK ENCEPHALOPATHY TSE PRION DISEASE SURVEILLANCE AND TESTING http://transmissible-mink-encephalopathy.blogspot.com/2017/07/mink-farming-usa-transmissible-mink.html tss
The occurrence of multiple strains of prions may reflect conformational variability of PrPSc, a disease-associated, aggregated variant of the cellular prion protein, PrPC. Here we used luminescent conjugated polymers (LCPs), which emit conformation-dependent fluorescence spectra, for characterizing prion strains. LCP reactivity and emission spectra of brain sections discriminated among four immunohistochemically indistinguishable, serially mouse-passaged prion strains derived from sheep scrapie, chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), and mouse-adapted Rocky Mountain Laboratory scrapie prions. Furthermore, using LCPs we differentiated between field isolates of BSE and bovine amyloidotic spongiform encephalopathy, and identified noncongophilic deposits in ...
This category includes disorders caused by prions, which are infectious proteins. Examples of the transmissible spongiform encephalopathies they cause include Creutzfeldt-Jakob Syndrome, Bovine Spongiform Encephalopathy, Gerstmann-Straussler-Scheinker Disease, Kuru, Scrapie in sheep and goats, Chronic Wasting Disease of cervids, Transmissible Mink Encephalopathy, and Fatal Familial Insomnia.
Definition of Prion disease in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is Prion disease? Meaning of Prion disease as a legal term. What does Prion disease mean in law?
Creutzfeld-Jakob disease (CJD) is the most common human prion disease. This disease is different from vCJD since it is not acquired and is either sporadic or inherited. CJD has an annual incidence of approximately one case per million in a population. This means that, in the United States, approximately 300 cases may occur per year. While duration of the disease can vary, CJD is usually fatal within a year-or within a matter of months. Other human prion diseases include Gerstmann-Straussler-Scheinker disease (GSS), fatal familial insomnia (FFI), and Kuru. GSS and FFI are genetic and inherited in an autosomal dominant manner. In contrast, Kuru is a prion disease often associated with cannibalistic practices. The disease was transmitted amongst members of the Fore people in New Guinea when they consumed brain tissues of infected, deceased family members. Other ...
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative diseases affecting the central nervous system. According to the prion hypothesis, TSEs are caused by proteinaceous infectious particles ("prions") that consist essentially of PrPSc, an aberrant form of the prion protein with a pathologically altered folding and/or aggregation structure. Scrapie of sheep, chronic wasting disease (CWD) of deer, bovine spongiform encephalopathy (BSE) of cattle, and variant Creutzfeldt-Jakob disease (vCJD) of humans are prominent examples of acquired prion diseases. To further pinpoint the peripheral tissues that could serve as reservoirs of prions in the mammalian body and from ...
Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the "scrapie form" (PrPSc), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of ...
Many neurodegenerative diseases are characterized by the deposition of misfolded protein aggregates. Therefore, it is suggested that these diseases share the involvement of similar cellular signalling mechanisms associated with protein folding and clearance. Previously, we have demonstrated increased presence of several UPR activation markers, including pPERK and pIRE1α, in post-mortem brain tissue of AD, FTLD-tau and PD [24, 40, 41]. In the present study, we aimed to further elucidate the involvement of the UPR in human prion pathology. To this end, we selected cases from the Dutch cohort of human prion disease patients [29] and performed immunohistochemistry to visualize UPR activation markers on post-mortem frontal cortex sections. Immunoreactivity for pIRE1α and pPERK was not increased in human ...
Ataxia is common in various forms of human prion diseases but there is a dearth of validated assessment tools and data on the subject. Originally used for inherited cerebellar ataxias, the Scale for Assessment and Rating of cerebellar Ataxia (SARA) and Composite Cerebellar Functional Severity Score (CCFS) have been incorporated into the National Prion Monitoring Cohort (NPMC) as semi-quantitative measures of posture, gait, kinetic dysfunction and speech in patients with sporadic and inherited Creutzfeldt-Jakob disease (CJD).. SARA and CCFS assessments were completed for patients with sporadic CJD (sCJD, n=119), and inherited prion disease (IPD, n=46). Patients were concurrently scored on the Medical Research Council Prion Disease Rating Scale (MRC PDRS), a functionally-oriented measure of disease progression validated in CJD patients.. SARA ...
Prion diseases are caused by the accumulation of an aberrantly folded isoform of the prion protein, designated PrPSc. In a cell-based assay, quinacrine inhibits the conversion of normal host prion protein (PrPC) to PrPSc at a half-maximal concentration of 300 nM. While these data suggest that quinacrine may be beneficial in the treatment of prion disease, its penetration into brain tissue has not been extensively studied. If quinacrine penetrates brain tissue in concentrations exceeding that demonstrated for in vitro inhibition of PrPSc, it may be useful in the treatment of prion disease. Oral quinacrine at doses of 37.5 mg/kg/D and 75 mg/kg/D was administered to mice for 4 consecutive weeks. Plasma and tissue (brain, liver, spleen) samples were taken over 8 weeks: 4 weeks ...
The bovine spongiform encephalopathy (BSE) agent has been transmitted to humans, leading to variant Creutzfeldt-Jakob disease. Sheep and goats can be experimentally infected by BSE and have been potentially exposed to natural BSE; however, whether BSE can be transmitted to small ruminants is not known. Based on the particular biochemical properties of the abnormal prion protein (PrPsc) associated with BSE, and particularly the increased degradation induced by proteinase K in the N terminal part of PrPsc, we have developed a rapid ELISA designed to distinguish BSE from other scrapie strains. This assay clearly discriminates experimental ovine BSE from other scrapie strains and was used to screen 260 transmissible spongiform encephalopathy (TSE)-infected small ruminant samples identified by the French active surveillance network (2002/2003). In this context, this test has helped to identify the first case of natural BSE in a ...
Bovine spongiform encephalopathy (BSE) can be efficiently transmitted to small ruminants (sheep and goats) with certain prion protein (PrP) genotypes. Polymorphisms in PrP of both the host and donor influence the transmission efficiency of transmissible spongiform encephalopathies (TSEs) in general. These polymorphisms in PrP also modulate the PrP conversion underlying TSE agent replication. Here we demonstrate that single-round protein misfolding cyclic amplification (PMCA) can be used to assess species and polymorphism barriers at the molecular level. We assessed those within and between the ovine and bovine species in vitro using a variety of natural scrapie and experimentally generated cross-species BSE agents. These BSE agents include ovBSE-ARQ isolates (BSE derived from sheep having the ARQ/ARQ PrP genotype), and two unique BSE-derived variants: BSE passaged in VRQ/VRQ sheep and a cow BSE agent isolate generated by back-transmission of ...
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Citation: Herrmann, L.M., Cheevers, W.P., Davis, W.C., Knowles, Jr., D.P., ORourke, K.I. 2005. CD21 positive follicular dendritic cells: A possible source of PrPSc in lymph node macrophages of scrapie-infected sheep. American Journal of Pathology. 162(4):1075-1081. Interpretive Summary: Natural sheep scrapie is part of a group of neurodegenerative diseases called transmissible spongiform encephopathies (TSEs) and continues to be spread in flocks in the United States. The presence of prion protein (PrPSc) in germinal centers of lymphoid tissues of scrapie-infected sheep is a marker for scrapie. But, little information exists regarding the specific cell types in lymphoid tissue that accumulate PrPSc. Using dual immunohistochemistry, follicular macrophages cells involved in the immune response of lymph nodes from scrapie-infected sheep were found to accumulate PrPSc. Technical Abstract: Natural sheep scrapie is a ...
CiteSeerX - Document Details (Isaac Councill, Lee Giles, Pradeep Teregowda): Abstract. The misfolded form of cellular prion protein (PrPC) is the main component of the infectious agent of transmissible spongiform encephalopathies and the validated biomarker for these diseases. The expression of PrPC is highest in the central nervous system and has been found in peripheral tissues. Soluble PrPC has been detected in cerebrospinal fluid, urine, serum, milk, and seminal plasma. In this study, attempts were made to characterize prion protein in urine samples from normal and scrapie-infected sheep. Urine samples from scrapie-infected sheep and age-matched healthy sheep were collected and analyzed by Western blot following concentration. A protease K-sensitive protein band with a molecular weight of approximately 27-30 kDa was visualized after immunoblotting with anti-PrP ...
... : A Coggle Diagram about INHERITED DISEASES (However this doesnt stop it from inducing misfolding in at least one other protein, which then triggers faster propagation, only 5% of CJD cases, primary sequence mutations destabilizes alpha helical structure of PrP-C, protein encouraged to misfold into form rich in Beta sheets b/c relatively more stable, First misfolded PrP-Sc goes on to induce more misfoldings -| plaques build up in the brain, BUT initial mutation makes it harder for first PrP-Sc to have affinity w/ cellular forms, 85% from random mutations rather than mutations from parents, ~30 PRNP gene mutations linked to inherited prion disease, including point mutations, insertions, stop codons, diff. mutations can lead to same disease, Octarepeat inserts dont cause disease, but make you more susceptible to developing certain diseases, loss of H-bonding and salt bridges in unstructured 1st half of ...
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This documentary deals with a very rare and unusual prion disease called Fatal Familial Insomnia or FFI for short. FFI is a prion disease that targets the thalamus, of which of its many functions ...
Prions, infectious agents causing transmissible spongiform encephalopathy (TSE), are composed primarily of the pathogenic form (PrPSc) of the host-encoded prion protein. Although very low levels of infectivity have been detected in urine from scrapie-infected rodents, no reports of urinary PrPSc have been substantiated. Studies on the dynamics of urinary PrPSc during infection are needed to ensure the safety of urine-derived biopharmaceuticals and to assess the possible horizontal transmission of prion diseases. Using the protein misfolding cyclic amplification technique, a time-course study of urinary excretion and blood levels of PrPSc was performed in Sc237-infected hamsters and a high rate of PrPSc excretion was found during the terminal stage of the disease. Following oral administration, PrPSc was present in all buffy coat samples examined; it was also ...
Prion diseases are neurodegenerative diseases with a fatal course affecting both humans and animals. The Creutzfeldt-Jakob disease of man and the scrapie of sheep and goats are the diseases known for a long time. To these it was added in the 80s the bovine spongiform encepalopathy, the so-called "mad cow" that, in 2001 - following the demonstration of its transmissibility to humans - caused one of the most serious food crises that have ever been recorded globally.. The neurological symptoms observed in the dromedaries, reminiscent of those of the "mad cow", have made the Algerian researchers suspect that it could be a prion disease. The laboratory investigations conducted by the group of researchers of the Istituto Superiore di Sanità confirmed the suspicion. The new disease has been called Camel Prion Disease . The ...
Protein aggregation is the cause of several human diseases such as diabetes mellitus type 2, Parkinson s disease, Alzheimer s disease, Huntington s disease, spongiform encephalopathies, congestive heart failure or dialysis-related amyloidosis. All of these disorders result from protein misfolding which leads to fibrillization and deposition of amyloid plaques in different parts of the body.Due to high molecular weight of the amyloid fibrils and intrinsic heterogeneity of the intermediate states, protein aggregation is a very challenging field of study for the structural biologist. However, nuclear magnetic resonance (NMR) provides a unique possibility to investigate aggregation at all stages, from the monomer to the fibrils.In this work, structural changes involved in prion diseases and dialysis-related amyloidosis are investigated with the help of various NMR ...
Groundbreaking research from the University of Alberta has identified the structure of the infectious prion protein, the cause of "mad cow disease" or BSE, chronic wasting disease in deer and elk and Creutzfeldt-Jakob disease in humans, which has long remained a mystery.. The infectious prion protein is a misfolded protein, which makes it very difficult to purify and study. Since it clumps together, standard structural biology techniques cannot be used to study it. Since the protein was first purified in the 1980s researchers have made limited insights into the structure of the protein.. The collaborative study, published in PLOS Pathogens, used electron cryomicroscopy to collect high-resolution electron micrographs. This was the first time this technology has been used on amyloid fibrils of the infectious ...
Spiroplasma, small motile wall-less bacteria, are linked by molecular and serological studies to the transmissible spongiform encephalopathies (TSEs), which include scrapie in sheep, chronic wasting disease (CWD) in deer and Creutzfeldt-Jakob disease in humans. In this study, two experiments were undertaken to determine the role of spiroplasma in the pathogenesis of TSE. In experiment 1, Spiroplasma mirum, a rabbit tick isolate that had previously been shown to experimentally induce spongiform encephalopathy in rodents, was inoculated intracranially (IC) into ruminants. S. mirum-inoculated deer manifested clinical signs of TSE after 1.5 to 5.5 months incubation. The deer, as well as sheep and goats, inoculated with S. mirum developed spongiform encephalopathy in a dose-dependent manner. In experiment 2, spiroplasma closely related to S. mirum were isolated from TSE-affected brains via passage in embryonated eggs, and propagated in cell-free M1D media. Spiroplasma spp. isolates from ...
Prion diseases are fatal neurodegenerative diseases characterized by the accumulation of PrPSc, the infectious and protease-resistant form of the cellular prion protein (PrPC). We generated lentivectors expressing PrPC-specific short hairpin RNAs (shRNAs) that efficiently silenced expression of the prion protein gene (Prnp) in primary neuronal cells. Treatment of scrapie-infected neuronal cells with these lentivectors resulted in an efficient and stable suppression of PrPSc accumulation. After intracranial injection, lentiviral shRNA reduced PrPC expression in transgenic mice carrying multiple copies of Prnp. To test the therapeutic potential of lentiviral shRNA, we used what we believe to be a novel approach in which the clinical situation was mimicked. We generated chimeric mice derived from ...
Prion diseases are fatal neurodegenerative diseases characterized by the accumulation of PrPSc, the infectious and protease-resistant form of the cellular prion protein (PrPC). We generated lentivectors expressing PrPC-specific short hairpin RNAs (shRNAs) that efficiently silenced expression of the prion protein gene (Prnp) in primary neuronal cells. Treatment of scrapie-infected neuronal cells with these lentivectors resulted in an efficient and stable suppression of PrPSc accumulation. After intracranial injection, lentiviral shRNA reduced PrPC expression in transgenic mice carrying multiple copies of Prnp. To test the therapeutic potential of lentiviral shRNA, we used what we believe to be a novel approach in which the clinical situation was mimicked. We generated chimeric mice derived from ...
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy, or prion disease, that affects deer, elk, and moose. Human susceptibility to CWD remains unproven despite likely exposure to CWD-infected cervids. We used 2 nonhuman primate species, cynomolgus macaques and squirrel monkeys, as human models for CWD susceptibility. CWD was inoculated into these 2 species by intracerebral and oral routes. After intracerebral inoculation of squirrel monkeys, 7 of 8 CWD isolates induced a clinical wasting syndrome within 33-53 months. The monkeys brains showed spongiform encephalopathy and protease-resistant prion protein (PrPres) diagnostic of prion disease. After oral exposure, 2 squirrel monkeys had PrPres in brain, spleen, and lymph nodes at 69 months postinfection. In contrast, cynomolgus macaques have not shown evidence of clinical ...
Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial Protein Misfolding Cyclic Amplification (sPMCA) have suggested that objects on a scrapie-affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation sheep became infected when exposed to either a water ...
Introduction). Variant Creutzfeldt-Jakob disease (vCJD) was identified in 1996 as distinct from classical forms of CJD (both sporadic and familial).1 Cumulative evidence strongly supports that vCJD is zoonotically linked to bovine spongiform encephalopathy (BSE).2-4 BSE, CJD, and vCJD are transmissible spongiform encephalopathies (TSEs), a family of invariably fatal neurodegenerative diseases affecting both humans and animals.5 They are associated with the accumulation in affected brains of misfolded, protease resistant conformers (PrPres) of a normal host protein known as the prion protein. There is currently no proven prophylaxis or effective treatment for any form of CJD. The molecular structure of the infectious agent is unknown but is referred to as a prion.2,6 Soon after the recognition of vCJD, the tissue distribution of the disease-associated PrPres ...
Pathogenesis and transmission of the prion disorders (transmissible spongiform encephalopathies, TSEs) are mediated by a modified isoform of the prion protein (PrP). Prion protein gene (PRNP) alleles associated with relative susceptibility to TSE have been identified in sheep, humans and possibly elk. Comparable data have not been derived for mule deer, a species susceptible to the TSE chronic wasting disease (CWD). Initial analysis of the open reading frame (ORF) in exon 3 of the mule deer PRNP gene revealed polymorphisms in all 145 samples analyzed, with 10 potential polymorphic sites. Because 144/145 (99.3%) of the samples were heterozygous for a coding change (N/ S) at codon 138 (bp 412) and a non-coding polymorphism at bp 418, and individual deer with three or four different alleles were identified a possible gene duplication was indicated. Analysis of ...
Prion protein is the causative agent of the transmissible spongiform encephalopathies. According to the "prion hypothesis," the infectious isoform of prion protein, termed PrPSc, replicates by interacting with cellular PrPC and mediating its conformational change into the disease-causing PrPSc (19). Compared with its well-defined pathological significance, the physiological function of PrPC remains unclear. PrPC is highly expressed not only by cells in the CNS but also by follicular DCs, mature myeloid cells, and activated T cells. This distribution suggests involvement of PrPC in immune surveillance (20).. Our present study defines a novel role for PrPC as an M-cell receptor for the uptake of pathogenic bacteria. PrPC on macrophages has been reported to recognize surface-exposed Hsp60 of B. abortus and to facilitate internalization of the bacteria (13); however, Fontes et ...
Bovine Spongiform Encephalopathy is a progressive, fatal disease of the nervous system of cattle. It is what is known as a transmissible spongiform encephalopathy (TSE).
Prion diseases are classically characterized by the accumulation of pathological prion protein (PrPSc) with the protease resistant C-terminal fragment (PrPres) of 27-30 kDa. However, in both humans and animals, prion diseases with atypical biochemical features, characterized by PK-resistant PrP internal fragments (PrPres) cleaved at both the N and C termini, have been described. In this study we performed a detailed comparison of the biochemical features of PrPSc from atypical prion diseases including human Gerstmann-Sträussler-Scheinker disease (GSS) and variably protease-sensitive prionopathy (VPSPr) and in small ruminant Nor98 or atypical scrapie. The kinetics of PrPres production and its cleavage sites after PK digestion ...
IMPORTANCE: The diagnosis of autoimmune and neurodegenerative conditions can be unclear. Treatments such as removing the associated tumor, if present, and immunosuppression can halt or often reverse the progression of autoimmune conditions, but there is no curative treatment for neurodegenerative conditions. The presence of autoantibodies can sometimes be misleading. This report illustrates potential difficulties in differentiating autoimmune encephalopathies from sporadic Creutzfeldt-Jakob disease. OBSERVATIONS: In a clinical follow-up of an older man with rapidly evolving encephalopathy at a neuroscience center, unsuccessful treatment with immunosuppression based on the incorrect presumptive diagnosis of Morvan syndrome was followed by the correct histological diagnosis of sporadic Creutzfeldt-Jakob disease. CONCLUSIONS AND RELEVANCE: Autoimmune encephalopathies raise important treatment options and potential for recovery. However, since neuronal antibodies may be positive in ...
Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest form of human prion diseases, accounting for about 85% of all cases. Current criteria for intra vitam diagnosis include a distinct phenotype, periodic sharp and slow-wave complexes at electroencephalography (EEG), and a positive 14-3-3-protein assay in the cerebrospinal fluid (CSF). In sCJD, the disease phenotype may vary, depending upon the genotype at codon 129 of the prion protein gene (PRNP), a site of a common methionine/valine polymorphism, and two distinct conformers of the pathological prion protein. Based on the combination of these molecular determinants, six different sCJD subtypes are recognized, each with distinctive clinical and pathologic phenotypes. We analyzed CSF samples from 127 subjects with definite sCJD to assess the diagnostic value of 14-3-3 ...
An autosomal dominant familial prion disease with a wide spectrum of clinical presentations including ATAXIA, spastic paraparesis, extrapyramidal signs, and DEMENTIA. Clinical onset is in the third to sixth decade of life and the mean duration of illness prior to death is five years. Several kindreds with variable clinical and pathologic features have been described. Pathologic features include cerebral prion protein amyloidosis, and spongiform or neurofibrillary degeneration. (From Brain Pathol 1998 Jul;8(3):499-513; Brain Pathol 1995 Jan;5(1):61-75 ...
Sunday, February 2, 2014 The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy NOTE Pathology http://bovineprp.blogspot.com/2014/02/the-presence-of-disease-associated.html kind regards,
Introduction. Scrapie is a fatal, infectious neurodegenerative disease that affects sheep and goats. The disease results from infection with pathogenic agents known as "prions" which change the normal prion protein (PrPC) to the improperly folded, disease-associated form (PrPSc). The abnormal PrPSc is resistant to the protein turnover process and forms deposits in the central nervous system and some peripheral tissues that lead to progressive neurodegeneration. Goat scrapie is similar to a group of prion diseases that includes Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE) in cattle, sheep scrapie and chronic wasting disease in cervids. The disease impacts animal health and welfare, animal movement and trade. Natural mutations (also called variants or alleles) in the prion ...
Prions are misfolded proteins that propagate by corrupting properly folded versions of themselves. The prion protein PrP (known as PrPSC in its misfolded form) causes deadly transmissible spongiform encephalopathies, including bovine spongiform encephalopathy (BSE) in cows, scrapie in sheep, and Creutzfeldt-Jakob disease (CJD) in humans. PrPSC molecules attach to and convert normal PrP proteins into the toxic form, accelerating the formation of PrPSC aggregates and fibrils. When these aggregates break apart, each fragment becomes a seed that can corrupt new PrP molecules. This break-up process is what senior author Adriano Aguzzi of the University of Zurich aimed to target. "That is the most important moment in the life of a prion fibril, just like mitosis is for a cancer cell," Aguzzi told Alzforum. As his weapon of choice, Aguzzi chose a ...
Variant Creutzfeldt-Jakob disease is almost certainly caused by the bovine spongiform encephalopathy agent, and although the disease is rare (115 deaths to date) there is uncertainty about future numbers of cases.1 The lack of a conventional immune response and the inability to detect abnormal prion protein in blood has hampered the development of a blood test.1 Lymphoreticular accumulation of prion protein has been used as a preclinical test for scrapie (the form of the disease in sheep and goats) and is a consistent feature of variant Creutzfeldt-Jakob disease, occurring before the onset of symptoms.2-4 We screened large numbers of specimens from appendicectomies and tonsillectomies for the presence of prion protein in lymphoreticular tissue to determine the number of people with preclinical variant Creutzfeldt-Jakob disease. ...
The objective of this project was to develop an efficient immuno-slotblotting technique that could be used as a quantitative assay in measuring the effects of Protein Disulfide Isomerase (PDI) on prion protein misfolding in Chronic Wasting Disease (CWD). Chronic Wasting Disease is a transmissible spongiform encephalopathy that is horizontally transmitted amongst families of cervids, which includes elk, deer, and moose. The infectious agent in CWD is a misfolded prion protein that comes into contact with other prion proteins, causing them to misfold. Previous observations have suggested that disulfide bond rearrangement may be an important step in the misfolding process. In order to measure rates of prion misfolding, a method must be developed to detect the prion ...
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy afflicting the Cervidae family in North America, causing neurodegeneration and ultimately death. Although there are no reports of natural cross-species transmission of CWD to noncervids, infected deer carcasses pose a potential risk of CWD exposure for other animals. We placed 40 disease-free white-tailed deer (Odocoileus virginianus) carcasses and 10 gut piles in the CWD-affected area of Wisconsin (USA) from September to April in 2003 through 2005. We used photos from remotely operated cameras to characterize scavenger visitation and relative activity. To evaluate factors driving the rate of carcass removal (decomposition), we used Kaplan-Meier survival analysis and a generalized linear mixed model. We recorded 14 species of scavenging mammals (6 visiting species) and 14 species of scavenging birds (8 visiting species). Prominent scavengers included American crows (Corvus brachyrhynchos), raccoons (Procyon lotor), and ...
At a World Health Organization (WHO) Consultation organized in Geneva on April 2-3, 1996, a group of international experts reviewed the public health issues related to bovine spongiform encephalopathy (BSE) and the emergence of a new variant of Creutzfeldt-Jakob Disease (V-CJD), as officially reported by the United Kingdom on March 20, 1996. The Consultation made recommendations, based on the latest scientific information, to minimize transmission of BSE among animals and to reduce as completely as possible any exposure of humans to the BSE agent. FINDINGS Bovine Spongiform Encephalopathy BSE is a transmissible spongiform encephalopathy (TSE) in cattle, which was first identified in the United Kingdom in 1986. It is one of a group of similar degenerative diseases that occur in several animal species. Transmission of BSE to cattle appears to have occurred by contaminated meat and bone meal in concentrate feed, sheep or cattle being the original source. The United Kingdom is ...
Chronic Wasting Disease (CWD) is an infectious, degenerative disease of animals in the family cervidae (elk, deer, and moose, etc.) that causes brain cells to die, ultimately leading to the death of the affected animal. First recognized in Colorado in 1967, CWD was described as a clinical wasting syndrome of unknown cause. It later became clear that CWD was a member of a group of diseases known as transmissible spongiform encephalopathies or TSEs. TSEs include a number of different diseases that affect animals or humans, including bovine spongiform encephalopathy (BSE or "mad cow") in cattle, scrapie in sheep and goats, and Creutzfeldt-Jacob disease (CJD), variant CJD, Kuru, fatal familial insomnia, and Gerstmann-Straussler-Scheinker syndrome in humans. Unlike other infectious diseases, TSEs are not caused by bacteria or viruses, but rather by a naturally occurring protein, that when folded incorrectly, ...
This category is for sites related to prion diseases such as Bovine Spongiform Encephalopathy (BSE) a.k.a. Mad Cow Disease, Creutzfeldt-Jakob Disease (CJD), Scrapie, Gerstmann-Sträussler-Scheinker disease, and other related infectious illnesses.
Age at disease onset and rate of progression of transmissible spongiform encephalopathies in man, sheep and mice are modulated by the host genome, in particular by the PrP gene and its allelic forms. Analysis of the caprine PrP gene revealed several different alleles. Four PrP protein variants were found, three of which were goat specific with single amino acid changes at codons 142, 143 and 240. The fourth was identical to the most common sheep PrP protein variant (Ala136-Arg154-Gln171). The dimorphism at codon 142 (Ile → Met) appeared to be associated with differing disease incubation periods in goats experimentally infected with isolates of bovine spongiform encephalopathy, sheep scrapie CH1641 or sheep-passaged ME7 scrapie.
As for the variance between the presence of PrPsc deposits and presentation of clinical signs found in some mice, PrPsc concentration used for inoculation could affect the results but also other explanations arise on this matter [42]. The possibility of a transmission of the disease without neurological signs [43] or a possible non-exclusive relationship between PrPsc and infectivity [44-46] and neurodegeneration [47], among them. Besides, the demonstration of the existence of animals as persistent carriers [48] or with a subclinical state of the disease [47], already described in mice with high titers of infection but no symptoms [49], should be borne in mind. This same lack of correlation between PrPsc and infectivity could be reflecting in the animals with symptoms but no PrPsc deposits [50], considering in this case that the disease might be transmitted without detectable PrPsc [44], even with high titers [51]. Further studies with non-diagnostic aims but for identification of astrocytes ...
Supplementary MaterialsFigure S1: PrPC in PMCA substrate prepared using brain from different mouse lines. infected individuals the prevalence of the disease in the population remains uncertain. In that context, the risk MK-0822 reversible enzyme inhibition of vCJD blood borne transmission is considered as a serious concern by health authorities. In this study, appropriate conditions and substrates for highly efficient and specific amplification of vCJD/BSE agent using Protein Misfolding Cyclic Amplification (PMCA) were first identified. This showed that whatever the origin (species) of the vCJD/BSE agent, the ovine Q171 PrP substrates provided the very best amplification shows. These outcomes indicate the fact that homology of PrP amino-acid series between your seed as well as the substrate isnt the key determinant from the vCJD agent propagation amplification of vCJD agent by Proteins Misfolding Cyclic Amplification (PMCA). In vCJD pet versions (sheep and primate), the ...
Looking for online definition of Creutzfeldt-Jakob disease in the Medical Dictionary? Creutzfeldt-Jakob disease explanation free. What is Creutzfeldt-Jakob disease? Meaning of Creutzfeldt-Jakob disease medical term. What does Creutzfeldt-Jakob disease mean?
We now show that a protease-resistant PrP isoform can also be detected in the urine of hamsters, cattle, and humans suffering from transmissible spongiform encephalopathies. Most important, this PrP isoform (UPrPSc) was also found in the urine of hamsters inoculated with prions long before the appearance of clinical signs. Interestingly, intracerebrally inoculation of hamsters with UPrPSc did not cause clinical signs of prion disease even after 270 days, suggesting it differs in its pathogenic properties from brain PrPSc. We propose that the detection of UPrPSc can be used to diagnose humans and animals incubating prion diseases, as well as to increase our understanding on the metabolism of PrPSc in vivo ...
Researchers from the University of Edinburgh have developed a new system to study Creutzfeldt-Jakob disease (CJD) in vitro. The work, funded by an NC3Rs project grant, has been published in The Journal of Experimental Medicine. CJD is a fatal neurodegenerative condition associated with misfolding of the normal form of the prion protein, similar to Bovine Spongiform Encephalopathy (BSE) in cows and Chronic Wasting Disease in deer. Until now, the main way to study the human form of the disease has been in animals, including in transgenic mice, sheep and non-human primates. These animal transmission studies are inherently variable, require large numbers of animals and can be assosiated with significant levels of suffering. The absence of a more relevant, human cell culture model which replicates human prions has hampered prion ...
Prions are abnormal and infectious forms of proteins that collect in brain tissue, causing cells to die. The sponge-like holes left in the brain are a hallmark of transmissible spongiform encephalopathies such as bovine spongiform encephalopathy (BSE, also known as mad cow disease in cows and Chronic Wasting Disease in deer and elk) and Creutzfeldt-Jakob disease (CJD), the
This is the first time CWD has been detected in the wild, west of the Continental Divide in Montana.. CWD is a progressive, fatal disease affecting the nervous system of mule deer, white-tailed deer, elk and moose. It is part of a group of diseases called Transmissible Spongiform Encephalopathies (TSEs). TSEs are caused by infectious, mis-folded prion proteins, which cause normal prion proteins throughout a healthy animals body to mis-fold, resulting in organ damage and eventual death.. CWD is a slow-moving disease. However, left unmanaged, it could result in long-term population declines within affected herds. All the states and provinces that border Montana, other than Idaho and British Columbia, have found CWD in their wild cervids.. Best Choice Products Set of 2 Adjustable Zero Gravity Lounge Chair Recliners for Patio, Pool w/ Cup Holders - (Color). CWD was first found in wild deer in ...
The uptake of proteins from soil into plants has been documented for many years and we have been investigating the uptake of prions into plants in vitro. Using laser scanning confocal microscopy, we observed root uptake of fluorescently-tagged, abnormal prion protein in the model plant thale cress or mouse-eared cress (_Arabidopsis thaliana_), as well as the crop plants alfalfa (_Medicago sativa_), barley (_Hordeum vulgare_), and tomato _(Solanum lycopersicum_). Using serial protein misfolding cyclic amplification, a sensitive biochemical prion detection method, we have found evidence of prions in aerial tissues from these species, as well as maize (_Zea mays_). Both stems and leaves of _A. thaliana_ grown in culture media containing prions are infectious when injected into mice and oral ...
Lesion profiles are considered to be an important tool for the comparison of the various animal and human spongiform encephalopathies and to obtain information upon prion strain variations. Histological and immunohistochemical reactions (PrPsc, GFAP) in 13 brain areas at 4 levels in the brainstem from 135 BSE-positive and 45 BSE-negative cases were retrospectively evaluated. In this retrospective study a lesion profile based on histological features was worked out on the basis of BSE cases originating from Switzerland over a period of ten years. They were confirmed post mortem by histology and immunohistology. Our findings were reviewed in comparison with lesion profiles published in England. No striking differences comparing type and quality of lesions in the relevant areas between the Swiss and the English cases were evident. Moreover, the lesion profiles and the character of the lesions did not differ between animals born before or after the offal feeding ...
Different is the case of vCJD. vCJD has been observed in 12 different countries, but in every registered case the same clinical and pathological characteristics have been found.39 In particular, the PrPSc responsible of the vCJD shows a peculiar WB profile, with the unglycosylated form of the protease-resistant PrPSc of 19 kDa (type 2) and a higher representation of the diglycosilated PrPSc (PrPSc 2B) compared with sCJD.39 Nevertheless, using specific antibodies against type 1 PrPSc, a small amount of PrPSc type 1 with a high percentage of diglycosilated form can be detected in association with PrPSc 2B.98 The 2B type is a useful marker for identifying the replication of BSE prions also in other species, including non-human primates.99 In addition, unlike sporadic and genetic CJD, in vCJD the same biological marker (2B type) has been found in all the analyzed brain areas.100 This strong biochemical and pathological homogeneity is in agreement with the ...
LONDON--The specter of a fatal disease that eats away brain tissue has scared up serious new money for European scientists. The European Commission today announced a $64 million research program on transmissible spongiform encephalopathies (TSEs), the family of neurodegenerative diseases that includes bovine spongiform encephalopathy (BSE)--popularly known as mad cow disease--and Creutzfeldt-Jakob disease in humans.. European research ministers had approved the program in early October, but a row ensued between commission officials and the French government over whether the money should come from current European Union research funds or from the commissions internal budget. The issue of funding, in fact, is not yet settled. The commission said today it has on hand $20 million for the program, and that the remaining $44 million must come from supplementary funds for the fourth European Framework Programme, which covers all European research spending from 1994 to 1998. The ...
Different is the case of vCJD. vCJD has been observed in 12 different countries, but in every registered case the same clinical and pathological characteristics have been found.39 In particular, the PrPSc responsible of the vCJD shows a peculiar WB profile, with the unglycosylated form of the protease-resistant PrPSc of 19 kDa (type 2) and a higher representation of the diglycosilated PrPSc (PrPSc 2B) compared with sCJD.39 Nevertheless, using specific antibodies against type 1 PrPSc, a small amount of PrPSc type 1 with a high percentage of diglycosilated form can be detected in association with PrPSc 2B.98 The 2B type is a useful marker for identifying the replication of BSE prions also in other species, including non-human primates.99 In addition, unlike sporadic and genetic CJD, in vCJD the same biological marker (2B type) has been found in all the analyzed brain areas.100 This strong biochemical and pathological homogeneity is in agreement with the ...
Different is the case of vCJD. vCJD has been observed in 12 different countries, but in every registered case the same clinical and pathological characteristics have been found.39 In particular, the PrPSc responsible of the vCJD shows a peculiar WB profile, with the unglycosylated form of the protease-resistant PrPSc of 19 kDa (type 2) and a higher representation of the diglycosilated PrPSc (PrPSc 2B) compared with sCJD.39 Nevertheless, using specific antibodies against type 1 PrPSc, a small amount of PrPSc type 1 with a high percentage of diglycosilated form can be detected in association with PrPSc 2B.98 The 2B type is a useful marker for identifying the replication of BSE prions also in other species, including non-human primates.99 In addition, unlike sporadic and genetic CJD, in vCJD the same biological marker (2B type) has been found in all the analyzed brain areas.100 This strong biochemical and pathological homogeneity is in agreement with the ...
Different is the case of vCJD. vCJD has been observed in 12 different countries, but in every registered case the same clinical and pathological characteristics have been found.39 In particular, the PrPSc responsible of the vCJD shows a peculiar WB profile, with the unglycosylated form of the protease-resistant PrPSc of 19 kDa (type 2) and a higher representation of the diglycosilated PrPSc (PrPSc 2B) compared with sCJD.39 Nevertheless, using specific antibodies against type 1 PrPSc, a small amount of PrPSc type 1 with a high percentage of diglycosilated form can be detected in association with PrPSc 2B.98 The 2B type is a useful marker for identifying the replication of BSE prions also in other species, including non-human primates.99 In addition, unlike sporadic and genetic CJD, in vCJD the same biological marker (2B type) has been found in all the analyzed brain areas.100 This strong biochemical and pathological homogeneity is in agreement with the ...
Stochastic computer simulations were used for quantifying the effect of selecting on prion protein (PrP) genotype on the risk of major outbreaks of classical scrapie and the rate of genetic progress in performance in commercial sheep populations already undergoing selection on performance. The risk of a major outbreak on a flock was measured by the basic reproduction ratio (R0). The effectiveness of different PrP selection strategies for reducing the population risk was assessed by the percentage of flocks with R0 , 1. When compared with the scenario where there was no selection on PrP genotype, selection against the VRQ allele had a minimal impact on genetic progress for performance traits. However, this strategy was not sufficient to eliminate the population risk after 15 years of selection when the initial frequency of the ARR allele was relatively low. More extreme PrP selection strategies aimed at increasing the frequency of the ARR allele and ...
Transmission of chronic wasting disease (CWD) between cervids is influenced by the primary structure of the host cellular prion protein (PrPC). In white-tailed deer, PRNP alleles encode the polymorphisms Q95 G96 (wild type [wt]), Q95 S96 (referred to as the S96 allele), and H95 G96 (referred to as the H95 allele), which differentially impact CWD progression. We hypothesize that the transmission of CWD prions between deer expressing different allotypes of PrPC modifies the contagious agent affecting disease spread. To evaluate the transmission properties of CWD prions derived experimentally from deer of four PRNP genotypes (wt/wt, S96/wt, H95/wt, or H95/S96), transgenic (tg) mice expressing the wt allele (tg33) or S96 allele (tg60) were challenged with these prion agents. Passage of deer CWD prions into tg33 mice resulted in ...
Interpretive Summary: Cases of bovine spongiform encephalopathy (BSE) or mad cow disease can be subclassified into at least 3 distinct disease forms with the predominate form known as classical BSE and the others collectively referred to as atypical BSE. Atypical BSE can be further subdivided into H-type and L-type cases that are distinct from classical BSE and from each other. Both of the atypical BSE subtypes are believed to occur spontaneously, whereas classical BSE is spread through feeding contaminated meat and bone meal to cattle. Transmissible mink encephalopathy (TME) is another prion disease that transmits to cattle and show similarities to L-type BSE when subjected to laboratory testing. The purpose of this study was to use non-human primates (cynomologous macaque) and transgenic mice expressing the human prion protein to determine if TME could represent a potential risk to ...
Kuru belongs to a class of diseases called transmissible spongiform encephalopathies (TSEs), also called prion diseases. It primarily affects the cerebellum - the part of your brain responsible for coordination and balance. Unlike most infections or infectious agents, kuru is not caused by a bacteria, virus, or fungus. Infectious, abnormal proteins known as prions cause kuru. Prions are not living organisms and do not reproduce. They are inanimate, misshapen proteins that multiply in the brain and form clumps, hindering normal brain processes.. Creutzfeldt-Jakob, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia are other degenerative diseases caused by prions. These spongiform diseases, as well as kuru, create sponge-like holes in your brain and are fatal. ...
This EFSA Scientific Report reviews and discusses the provisional results of a study (EURL/Cypriot study) on genetic resistance to Classical scrapie in goats in Cyprus. It is concluded that the provisional results obtained in the study further support the lower susceptibility to Classical scrapie in goats carrying the D146 and S146 alleles compared to wild type (N146N) goats. The results from intracerebral challenge are not compatible with a level of resistance as high as the one observed in sheep carrying the ARR allele or in goats carrying the K222 allele. Final results from the oral challenge will be crucial in determining the level of resistance associated with the D146 and S146 alleles. Furthermore, it is concluded that the provisional results obtained in the study are compatible with the possibility to use the D146 and S146 alleles to build a genetic strategy to control and eradicate Classical scrapie in goats in Cyprus. However, the success of such a strategy will be determined by the ...
Conformational intermediates of the human prion protein huPrPC were characterized by a combination of hydrostatic pressure (up to 200 MPa) with two-dimensional NMR spectroscopy. All pressure effects showed to be reversible and there is virtually no difference in the overall pressure response between the folded core of the N-terminal truncated huPrPC(121-230) and the full-length huPrPC(23-230). The only significant differences in the pressure response of full-length and truncated PrP suggest that E168, H187, T192, E207, E211 and Y226 are involved in a transient interaction with the unfolded N-terminus. High-pressure NMR spectroscopy indicates that the folded core of the human prion protein occurs in two structural states N1and N2 in solution associated with rather small differences in free enthalpies (3.0 kJ/mol). At atmospheric pressure approximately 29% of the ...
The Internets largest and most authoritative site for prions, mad cow disease (bovine spongiform encephalopathy or BSE), scrapie, Creutzfeldt-Jakob Disease (CJD and nvCJD), kuru,and chronic wasting disease (CWD). Over 6966 articles, updated twice weekly. General news, government cover-ups, prion molecular biology research developments. Color slides of spongiform brains; working links to online research journals and other mad cow sites worldwide.
Background: Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease of cattle. The bovine prion gene (PRNP) contains regions of both high and low linkage disequilibrium (LD) that appear to be conserved across Bos taurus populations. The region of high LD, which spans the promoter and part of intron 2, contains polymorphic loci that have been associated with classical BSE status. However, the complex genetic architecture of PRNP has not been systematically tested for an association with classical BSE. Methodology/Principal Findings: In this study, haplotype tagging single nucleotide polymorphisms (htSNPs) within PRNP were used to test for association between PRNP haplotypes and BSE disease. A combination of Illumina goldengate assay, sequencing and PCR amplification was used to genotype 18 htSNPs and 2 indels in 95 BSE case and 134 control animals. A haplotype within the region of high LD was found to be associated with ...
Prions have been responsible for an entire century of tragic episodes. Fifty years ago, kuru decimated the population of Papua New Guinea. Then, iatrogenic transmission of prions caused more than 250 cases of Creutzfeldt-Jakob disease. More recently, transmission of bovine spongiform encephalopathy to humans caused a widespread health scare. On the other hand, the biology of prions represents a fascinating and poorly understood phenomenon, which may account for more than just diseases and may represent a fundamental mechanism of crosstalk between proteins. The two decades since Stanley Prusiners formulation of the protein-only hypothesis have witnessed spectacular advances, and yet some of the most basic questions in prion science have remained unanswered. ...
Prion diseases are all, fortunately, rare. Unless we throw some cannibalism (actual or hi-tec) into the mix - then they can increase dramatically in prevalence. It seems likely that most, if not all, prion diseases occur as rare genetic mutations. I very briefly mentioned Fatal Familial Insomnia in class. This is an extremely rare prion disease caused by an inherited genetic mutation. The mutation responsible has been found in just 50 families worldwide. Although patients frequently do not show symptoms until middle age or later the subsequent progression into complete sleeplessness is untreatable, and ultimately fatal ...
Gerstman-Straussler-Scheinker syndrome is a hereditary prion pathology that bears a family character. Compared with Kreutzfeldt-Jakob disease, people of a younger age get sick (on average, Schlet earlier). The duration of the incubation period of Gerstman-Straussler-Scheinker syndrome varies between 5 ~ 30 years. Typical is the gradual loss of reflexes from the lower extremities, swallowing disorders, muscle hypotension, dysarthria, and dementia. The disease slowly progresses over 4-5 years and ends with the death of the patient. Diagnosis, treatment and prevention are similar to the measures used in the recognition and treatment of Kreutzfeldt-Jakob disease. Fatal Family Insomnia. Fatal familial insomnia is a hereditary prion disease described in 1986. as an autosomal dominant pathology and registered in people aged 25 to 70 years. The first manifestation is a progressive sleep disorder, accompanied by increased fatigue and not amenable to ...
High level contamination by natural and industrial sources of the alkali earth metal, barium (Ba) has been identified in the ecosystems/workplaces that are associated with high incidence clustering of multiple sclerosis (MS) and other neurodegenerative diseases such as the transmissible spongiform encephalopathies (TSEs) and amyotrophic lateral sclerosis (ALS). Analyses of ecosystems supporting the most renowned MS clusters in ... Massachusetts, Colorado, Guam, NE Scotland demonstrated consistently elevated levels of Ba in soils (mean: 1428 ppm) and vegetation (mean: 74 ppm) in relation to mean levels of 345 and 19 ppm recorded in MS-free regions adjoining. .... from the use of Ba as an atmospheric aerosol spray for enhancing/refracting the signalling of radio/radar waves along military jet flight paths, missile test ranges, etc. It is proposed that chronic contamination of the biosystem with the reactive types of Ba salts can initiate the pathogenesis of MS; due to the conjugation of Ba ...
Enzymatic Degradation of PrPSc by a Protease Secreted from Aeropyrum pernix K1. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
SAFEMEATs objectives when it comes to animal diseases involves minimising market disruption arising from the public health aspects of animal disease outbreaks and contributing, where appropriate, to the development and implementation of national policies and programs designed to protect Australia from exotic animal diseases. By focusing on this priority area, SAFEMEAT ensures the red meat sector is able to deal effectively with food safety issues arising from disease outbreaks in cattle, sheep or goats. SAFEMEAT also works to ensure Australias internationally recognised Transmissible Spongiform Encephalopathy (TSE) and Foot and Mouth Disease (FMD) free status is maintained by providing direction into the conduct of relevant projects and studies. Current initiatives include the National TSE Surveillance Program (NTSESP) which is nationally coordinated by Animal Health Australia (AHA). NTSESP involves identifying and testing cattle and sheep for clinical systems that could be ...
Bovine spongiform encephalopathy (BSE, often called mad cow disease) is a disease that causes brain changes and death in cattle. BSE does not occur in Australia. Overseas the disease has been shown to spread through meat products fed to cattle. New South Wales has banned the feeding of all animal products, including fish meals and feathers (called restricted animal material) to ruminant animals such as cattle, sheep, goats and deer. These bans provide insurance against any spread of the disease in Australia and satisfy the requirements of our meat export markets.. The contents of this Primefact include the following:. ...
CANADA - Alberta Agriculture and Rural Development and the Canadian Food Inspection Agency are reminding cattle producers in Alberta to call their veterinarians to collect brain tissue samples to be tested for bovine spongiform encephalopathy (BSE). Cattle producers play a key role in monitoring and eradicating this disease from the Canadian cattle herd by presenting eligible animals for testing. It is very important for us to test enough eligible samples to continue to demonstrate the low
Prions have a bad reputation. They are responsible for a variety of neurodegenerative diseases including Creutzfeldt-Jakob disease in humans and a plethora of spongiform encephalopathies in animals. But there may be more to neuronal prions than neurotoxicity. In the February 5 Cell, researchers led by Kausik Si at the Stowers Institute for Medical Research, Kansas City, Missouri, report that in the marine mollusk Aplysia Californica, prion-like activity of an RNA binding protein controls long-term facilitation (LTF), a strengthening of synaptic transmission that has been linked to memory formation. The protein oligomerizes into amyloid fibers when Aplysia sensory neurons are stimulated with serotonin and, in turn, the amyloid seems to strengthen LTF. This is the first example of eukaryotic prion activity ...
Cattle Importation. Guidelines for the Importation of Cattle (ruminants) into the United States (except from Canada and Mexico). Cattle from countries affected with bovine spongiform encephalopathy (BSE) OR foot-and-mouth disease (FMD, OR rinderpest are not permitted to be imported into the United States (see Country Disease List).. ** These are general requirements for importing cattle into the United States. You are advised to contact the National Import and Export Services at 301-851-3300 for the protocol to import cattle from a specific country.. Requirements:. ...
Animal health officials in Texas are watching with concern the relentless westward march of foot-and-mouth disease (FMD), the most recent outbreak of which was confirmed in late February at several sites in England, where livestock operations already have been financially ravaged by the brain-wasting disease, BSE (bovine spongiform encephalopathy) and outbreaks of the viral infection, hog cholera.
The Kveim test, Nickerson-Kveim or Kveim-Siltzbach test is a skin test used to detect sarcoidosis, where part of a spleen from a patient with known sarcoidosis is injected into the skin of a patient suspected to have the disease. If non caseating granulomas are found (4-6 weeks later), the test is positive. If the patient has been on treatment (e.g. glucocorticoids), the test may be false negative. The test is not commonly performed, and in the UK no substrate has been available since 1996. There is a concern that certain infections, such as bovine spongiform encephalopathy, could be transferred through a Kveim test. It is named for the Norwegian pathologist Morten Ansgar Kveim, who first reported the test in 1941 using lymph node tissue from sarcoidosis patients. It was popularised by the American physician Louis Siltzbach, who introduced a modified form using spleen tissue in 1954. Kveims work was a refinement of earlier studies performed by Nickerson, who in 1935 first reported on skin ...
Image source: Image Source. Researchers have developed a vaccination for chronic wasting disease (CWD) in deer. CWD is similar to mad cow disease in that both are caused by infectious proteins known as prions. Prions cause normal proteins primarily located on the surface of central nervous system cells to fold abnormally, resulting in the deterioration of neural tissue. The researchers developed the vaccine by placing a prion-like protein into the genome of a harmless Salmonella bacterium. The result was an immune response by the Salmonella bacteria that led to the production of anti-prion antibodies. The decision to select Salmonella bacteria was based on the bacterias ability to easily enter the gut and the fact that the most common method of infection is through the ingestion of ...
Sigma-Aldrich offers abstracts and full-text articles by [Kanella Prodromidou, Florentia Papastefanaki, Theodoros Sklaviadis, Rebecca Matsas].

Table 1 - Atypical Scrapie Prions from Sheep and Lack of Disease in Transgenic Mice Overexpressing Human Prion Protein - Volume...Table 1 - Atypical Scrapie Prions from Sheep and Lack of Disease in Transgenic Mice Overexpressing Human Prion Protein - Volume...

These data are consistent with the conclusion that prion disease is less likely to develop in humans after exposure to ... we inoculated transgenic mice that overexpressed human prion protein with brain tissue from sheep with natural field cases of ... We found that these mice were susceptible to BSE prions, but disease did not develop after prolonged postinoculation periods ... To investigate whether sheep infected with scrapie prions could be another source of infection, ...
more infohttps://wwwnc.cdc.gov/eid/article/19/11/12-1341-t1

Table 3 - Atypical Scrapie Prions from Sheep and Lack of Disease in Transgenic Mice Overexpressing Human Prion Protein - Volume...Table 3 - Atypical Scrapie Prions from Sheep and Lack of Disease in Transgenic Mice Overexpressing Human Prion Protein - Volume...

These data are consistent with the conclusion that prion disease is less likely to develop in humans after exposure to ... we inoculated transgenic mice that overexpressed human prion protein with brain tissue from sheep with natural field cases of ... We found that these mice were susceptible to BSE prions, but disease did not develop after prolonged postinoculation periods ... To investigate whether sheep infected with scrapie prions could be another source of infection, ...
more infohttps://wwwnc.cdc.gov/eid/article/19/11/12-1341-t3

Patent US6331296 - Food additives which affect conformationally altered proteins - Google PatentsPatent US6331296 - Food additives which affect conformationally altered proteins - Google Patents

The homogenate may be brain homogenate from a transgenic mouse infected with human prions. Compounds which are found to clear ... a disease associated with the conformationally altered protein. ... with test compound to determine if altered protein in the ... the altered protein are useful in preventing, arresting and/or reversing (i.e. treating) ... An assay comprises contacting cells containing a conformationally altered protein with test compound and determining if the ...
more infohttp://www.google.com/patents/US6331296?dq=6272333

Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of...Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of...

Recent observations have expanded the spectrum of prion diseases beyond the classically recognized forms. In the present study ... Light and electron microscopic immunostaining for the prion protein (PrP) revealed a peculiar intraneuritic distribution in ... with rapidly progressive dementia and may have implications for the understanding of the pathogenesis of prion diseases. ... indicative of the presence of disease-associated PrP (PrPSc) in these cases, when the results were compared with appropriate ...
more infohttps://actaneurocomms.biomedcentral.com/articles/10.1186/2051-5960-1-72

https://www.thefreelibrary.com/Detection+of+transmissible+spongiform+encephalopathies+using+proteins...-a099490578https://www.thefreelibrary.com/Detection+of+transmissible+spongiform+encephalopathies+using+proteins...-a099490578

Detection of transmissible spongiform encephalopathies using proteins found in serum and cerebrospinal fluid. (Medical Science ... These diseases are associated with the accumulation of a prion protein in nerve cells that lead to death of the host. The ... Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurologic diseases affecting both animals and humans ... demonstration that prions are responsible for BSE and can spread to humans has lead to urgency to develop early detection ...
more infohttps://www.thefreelibrary.com/Detection+of+transmissible+spongiform+encephalopathies+using+proteins...-a099490578

Daggett Research Group at the University of WashingtonDaggett Research Group at the University of Washington

December: Diverse Effects on the Native β-Sheet of the Human Prion Protein Due to Disease-Associated Mutations [DOI] ... September: Refolding the Engrailed Homeodomain: Structural Basis for the Accumulation of a Folding Intermediate [DOI] ... November: The influence of pH on the human prion protein: Insights into the early steps of misfolding [DOI] ... August: The consequences of pathogenic mutations to the human prion protein [DOI] ...
more infohttp://depts.washington.edu/daglab/pom.html

Sequestration of essential proteins causes prion associated toxicity in yeast - Vishveshwara - 2009 - Molecular Microbiology -...Sequestration of essential proteins causes prion associated toxicity in yeast - Vishveshwara - 2009 - Molecular Microbiology -...

These diseases are associated with the accumulation of the prion form of the PrP protein, PrPSc (Prusiner, 1982). Prions were ... such as Scrapie in sheep and Creuztfeldt-Jakob disease in humans (Prusiner, 1998). PrPSc is in a β-sheet rich, aggregated, ... Among these protein-misfolding diseases, prion diseases are unique as they are infectious. ... Prions are infectious, aggregated proteins that cause diseases in mammals but are not normally toxic in fungi. Excess Sup35p, ...
more infohttp://onlinelibrary.wiley.com/doi/10.1111/j.1365-2958.2009.06836.x/full

KAKEN - Research Projects | Studies on polymorphism of the prion protein gene in familial Creutzfeldt-Jakob disease. (KAKENHI...KAKEN - Research Projects | Studies on polymorphism of the prion protein gene in familial Creutzfeldt-Jakob disease. (KAKENHI...

The sequential development of abnormal prion protein accumulations in mice with Creutzfeldt-Jakob disease. Am. J. Pathol.. *. ... Publications] Ohgami T: Alzheimers amyloid precursor protein accumulates within axonal swellings in human brain lesions. ... These results imply that the primary structures of prion protein influence in the phenotype of prion protein disease, ... The sequencial development of abnormal prion protein accumulations in mice with CreutzfeldtーJakob disease. Am.J.Pathol.. *. ...
more infohttps://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02454245/

Isolated Cortical Signal Increase on MR Imaging as a Frequent Lesion Pattern in Sporadic Creutzfeldt-Jakob Disease | American...Isolated Cortical Signal Increase on MR Imaging as a Frequent Lesion Pattern in Sporadic Creutzfeldt-Jakob Disease | American...

... is a rare and fatal disease caused by the accumulation of abnormal/pathologic prion protein (PrPSc; Sc indicates scrapie) in ... Molecular genetics of human prion diseases in Germany. Hum Genet 1999;105:244-52. ... Six disease phenotypes (MM1, MM2, MV1, MV2, VV1, and VV2) defined by the codon 129 genotype (MM, MV, VV) of the prion protein ... Combined Diffusion Imaging and MR Spectroscopy in the Diagnosis of Human Prion Diseases ...
more infohttp://www.ajnr.org/content/29/8/1519.full

Therapy in Prion Diseases: From Molecular and Cellular Biology to Therapeutic Targets | Bentham ScienceTherapy in Prion Diseases: From Molecular and Cellular Biology to Therapeutic Targets | Bentham Science

Prion disorders are caused by the accumulation of an aberrantly folded isoform of the cellular prion protein (PrPc), commonly ... In human diseases, the manifestation can be sporadic, familial or acquired by infection. Prion disorders are caused by the ... Keywords: Prion diseases, prion protein, prion clearance, prion therapy, anti-prion drugs ... Keywords:Prion diseases, prion protein, prion clearance, prion therapy, anti-prion drugs ...
more infohttp://www.eurekaselect.com/83842

Sporadic Creutzfeldt-Jakob disease in 2 plasma product recipients, United Kingdom. - Free Online LibrarySporadic Creutzfeldt-Jakob disease in 2 plasma product recipients, United Kingdom. - Free Online Library

Emerging Infectious Diseases; Health, general Research Plasma products ... Sporadic Creutzfeldt-Jakob disease in 2 plasma product recipients, United Kingdom.(SYNOPSIS, Report) by ... B) Fine granular/ synaptic accumulation of abnormal prion protein in the cerebral cortex (case 1). 12F10 antiprion protein ... His primary research interests include human prion diseases. References (1.) Prusiner SB. Molecular biology of prion diseases. ...
more infohttps://www.thefreelibrary.com/Sporadic+Creutzfeldt-Jakob+disease+in+2+plasma+product+recipients%2C+...-a0499406145

SearchSearch

... infectious neurodegenerative disorders caused by the accumulation of aberrant prion proteins in the brain. TSEs can affect both ... Prion Diseases: Fatal and greatly feared. : A review of current knowledge, two and a half centuries after the 1st description ... Migraine is a disease where both environment and genetics play an important etiological role. It is a common disease, who ... Background: Fabry disease is a rare X-linked lysosomal storage disease caused by alpha-galactosidase A deficiency. Earlier it ...
more infohttps://www.duo.uio.no/handle/10852/212/discover?rpp=100&sort_by=dc.date.issued_dt&order=DESC

UCD Dublin | Research | Biomolecular & Biomed ScienceUCD Dublin | Research | Biomolecular & Biomed Science

Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein. ... Scrapie prion protein accumulation correlates with neuropathology and incubation times in hamsters and transgenic mice In: ... Transgenetics and gene targeting in studies of prion diseases In: Prusiner. S. B (eds). Prions Prions Prions. Berlin: Springer ... Molecular biology of prion propagation In: Morrison, D. R. O (eds). Prions and Brain Diseases in Animals and Humans. New York ...
more infohttp://www.ucd.ie/research/people/biomolecularbiomedscience/professormikescott/

Deadly proteins: prions | www.scienceinschool.orgDeadly proteins: prions | www.scienceinschool.org

... mad cow disease in the 1980s and 90s, and the emergence of its human equivalent, variant Creutzfeld-Jacob disease, there has ... been a great deal of research into prions, the causative agents. Mico Tatalovic reviews the current state of knowledge. ... These diseases create large fluid-filled holes in the brain tissue because the accumulation of aberrant prions causes the ... there are still those who believe that prion diseases are actually caused by unconventional viruses and that prion proteins are ...
more infohttps://www.scienceinschool.org/2010/issue15/prions

Browsing Duke Scholarly Works by TitleBrowsing Duke Scholarly Works by Title

Prion diseases are linked to the accumulation of a misfolded isoform (PrP(Sc)) of prion protein (PrP). Evidence suggests that ... Early hematopoietic effects of chronic radiation exposure in humans.  Akleyev, AV; Akushevich, Igor; Dimov, GP; Ukraintseva, ... Early hematopoiesis inhibition under chronic radiation exposure in humans.  Akleyev, AV; Akushevich, Igor; Dimov, GP; ... Similar to humans, songbirds rely on auditory feedback to maintain the acoustic and sequence structure of adult learned ...
more infohttps://dukespace.lib.duke.edu/dspace/handle/10161/2840/browse?rpp=20&order=ASC&sort_by=1&etal=-1&type=title&starts_with=E

Browsing Duke Scholarly Works by TitleBrowsing Duke Scholarly Works by Title

Prion diseases are linked to the accumulation of a misfolded isoform (PrP(Sc)) of prion protein (PrP). Evidence suggests that ... Early hematopoietic effects of chronic radiation exposure in humans.  Akleyev, AV; Akushevich, Igor; Dimov, GP; Ukraintseva, ... Early hematopoiesis inhibition under chronic radiation exposure in humans.  Akleyev, AV; Akushevich, Igor; Dimov, GP; ... Similar to humans, songbirds rely on auditory feedback to maintain the acoustic and sequence structure of adult learned ...
more infohttps://dukespace.lib.duke.edu/dspace/handle/10161/2840/browse?rpp=20&sort_by=1&type=title&etal=-1&starts_with=E&order=ASC

Enzymatic function found?Enzymatic function found?

Prion diseases are marked by the cerebral accumulation of conformationally modified forms of the cellular prion protein (PrP(C ... Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem. 1995 Aug 11;270(32):19173-80. ... Prion protein expression in muscle cells and toxicity of a prion protein fragment. Eur J Cell Biol. 1998 Jan;75(1):29-37. ... Prion protein-overexpressing cells show altered response to a neurotoxic prion protein peptide. J Neurosci Res. 1998 Nov 1;54(3 ...
more infohttp://www.mad-cow.org/aug99_sci.html

New wonder-drug may prevent brain cells from dying - The Financial ExpressNew 'wonder-drug' may prevent brain cells from dying - The Financial Express

Scientists in the UK have discovered a drug that may safely help prevent neurodegenerative brain diseases such as Alzheimers ... Previously, the team found that the accumulation of misfolded proteins in mice with prion disease over-activates a natural ... "We know that trazodone is safe to use in humans, so a clinical trial is now possible to test whether the protective effects of ... Misfolded proteins build up in the brain in several neurodegenerative diseases and are a major factor in dementias such as ...
more infohttp://www.financialexpress.com/lifestyle/health/new-wonder-drug-may-prevent-brain-cells-from-dying/635078/

Frontiers | GRP78 at the Centre of the Stage in Cancer and Neuroprotection | NeuroscienceFrontiers | GRP78 at the Centre of the Stage in Cancer and Neuroprotection | Neuroscience

... is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is ... is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is ... The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, ... The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, ...
more infohttps://www.frontiersin.org/articles/10.3389/fnins.2017.00177/full

Prion Diseases | Johns Hopkins MedicinePrion Diseases | Johns Hopkins Medicine

A prion is a type of protein that can trigger normal proteins in the brain to fold abnormally. Prion diseases can affect both ... The most common form of prion disease that affects humans is Creutzfeldt-Jakob disease (CJD). ... humans and animals and are sometimes transmitted to humans by infected meat products. ... This abnormal accumulation of protein in the brain can cause memory impairment, personality changes, and difficulties with ...
more infohttps://www.hopkinsmedicine.org/health/conditions-and-diseases/prion-diseases

Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene | Acta...Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene | Acta...

Sporadic Creutzfeldt-Jakob Disease (CJD) is the most common human prion disease, accounting for approximately 85-90% of cases, ... misfolded prion protein known as scrapie prion protein (PrPSc). These disorders are unique as they occur as sporadic, genetic ... due to mutations in the prion protein gene (PRNP), account for 10-15% of cases. Genetic forms show a striking variability in ... the neuropathological analysis revealed diffuse synaptic type deposition of proteinase K-resistant prion protein (PrPres), and ...
more infohttps://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-018-0656-4

Giovanna Mallucci - WikipediaGiovanna Mallucci - Wikipedia

Previously, the team found that the accumulation of misfolded proteins in mice with prion disease over-activates a natural ... You dont know whats going to work in humans but it means we dont have to wait 20 years to find something." She added: "We ... Toxicology Unit in Leicester originally discovered that this accumulation of misfolded proteins in mice with prion disease over ... Misfolded proteins build up in the brain in several neurodegenerative diseases and are a major factor in dementias such as ...
more infohttps://en.wikipedia.org/wiki/Giovanna_Mallucci

Nerve tissue protein - WikipediaNerve tissue protein - Wikipedia

Neurodegenerative disease is caused by prions accumulation of PrPsc. The brains of humans or animals affected with prion ... Neuronal Apoptosis-Inhibitory Protein Neuronal Calcium-Sensor Proteins Neuropeptides Olfactory Marker Protein S100 Proteins ... Prion protein triggers are an important factor in the signals that ensure myelin maintenance and are distinct from those that ... Prion protein and antibodies POM1 and POM3, which recognize epitopes in the terminus (around amino acids (aa) 140-152) and ...
more infohttps://en.wikipedia.org/wiki/Nerve_tissue_protein

Biology-Online •Biology-Online •

Soon after the recognition of vCJD, the tissue distribution of the disease-associated PrPres of the prion protein was shown to ... a family of invariably fatal neurodegenerative diseases affecting both humans and animals.5 They are associated with the ... accumulation in affected brains of misfolded, protease resistant conformers (PrPres) of a normal host protein known as the ... The most common theory on the origins of BSE holds that it was originally transmitted to cows from a sheep prion disease, ...
more infohttps://www.biology-online.org/kb/revision.php?p_id=3373&a_id=1216

Print - Biology-OnlinePrint - Biology-Online

Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999;353: ... Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol 2004;203:733-9. Wells GA, Scott AC, ... 10 The first evidence for the transmissibility of human prion diseases was from kuru, a disease discovered in the late 1950s in ... Collinge J. Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 2001;24:519-50. Will RG, ...
more infohttp://www.biology-online.org/kb/print.php?aid=1216
  • Patient characteristics as well as electroencephalography, CSF, and codon 129 genotype of the prion protein gene ( PRNP ) were correlated with the most frequent MR imaging lesion patterns. (ajnr.org)
  • Six disease phenotypes (MM1, MM2, MV1, MV2, VV1, and VV2) defined by the codon 129 genotype (MM, MV, VV) of the prion protein gene ( PRNP ) and pathologic isotype of the PrP Sc type 1 or 2 have been recently described with distinctive neuropathologic features and various clinical and diagnostic findings. (ajnr.org)
  • Studies on polymorphism of the prion protein gene in familial Creutzfeldt-Jakob disease. (nii.ac.jp)
  • 1996) 'Transgenetics and gene targeting in studies of prion diseases' In: Prusiner. (ucd.ie)
  • 17- 19 It is also no longer assumed that vCJD affects only individuals who are homozygous for methionine at codon 129 of the prion protein gene (approximately 33% of the population), leading experts to wonder if the real epidemic is in fact ahead. (biology-online.org)
  • Understanding the genes that interact with a disease gene will shed light on the genetic pathway in which the disease gene acts. (nih.gov)
  • GSS, fCJD, and FFI are caused by mutations within the open reading frame of the human prion protein gene ( PRNP) (Fig. 1 ) and inherited as autosomal dominant traits. (biomedcentral.com)
  • Of course, the human prion gene repeat region provides a favorable mileau for slippage and interest in CJD has enabled an intensive screen. (mad-cow.org)
  • The basic idea is that as DNA replication procedes through the prion gene, the daughter strand experiences slippage facilitated by complementarity to an earlier template repeat. (mad-cow.org)
  • Progress of the replication fork may be affected by a unique feature of the prion gene, the conserved hairpin C whose function at the level of mRNA or DNA remains unknown. (mad-cow.org)
  • Specifically, two proteins, 14-3-3 (gamma isoform) and S-100, have been shown to be elevated in TSEs, such as Cruetzfelt-Jakob disease. (thefreelibrary.com)
  • In humans, TSEs also cause personality changes and depression, and sufferers may experience confusion, memory problems and insomnia. (scienceinschool.org)
  • However, three decades of subsequent investigations, pursued most notably by Stanley Prusiner, who was awarded the Nobel Prize in Physiology or Medicine in 1997 for his work with prions and TSEs, resulted in the wide acceptance of this 'protein-only hypothesis' w2 . (scienceinschool.org)
  • This toxicity is rescued by expressing the Sup35Cp domain of Sup35p, which is sufficient for cell viability but not prion propagation. (wiley.com)
  • 1998) 'Molecular biology of prion propagation' In: Morrison, D. R. O (eds). (ucd.ie)
  • Cell culture models were highly instrumental in uncovering fundamental aspects of prion propagation. (eurekaselect.com)
  • By examining the structure of the amyloids underlying most yeast prions, and the genetics of prion propagation and generation we have obtained an understanding of how proteins can be the basis of genetic information propagation, discovered several means of curing prions, and obtained information that will likely be useful in studies of human amyloidoses. (nih.gov)
  • Prions are the only known case of self-propagating pathogenic (disease-causing) proteins, and they are able to cause severe illness even though they seem to be just protein molecules: unlike bacteria, viruses or other known pathogens, they have no information encoded in nucleic acids (DNA or RNA) about how to invade and replicate within the host. (scienceinschool.org)
  • Our findings support a pathogenic role for the V189I PRNP variant, confirm the heterogeneity of the clinical phenotypes associated to PRNP mutations and highlight the importance of PrP Sc detection assays as diagnostic tools to unveil prion diseases presenting with atypical phenotypes. (biomedcentral.com)
  • Using mouse models, they described the pathogenic role of the unfolded protein response (UPR) in neurodegeneration, which led to the discovery of the first small molecule - an inhibitor of this pathway - to prevent neurodegeneration in vivo. (wikipedia.org)
  • 1999) 'Transmission and replication of prions' In: Prusiner, S. B (eds). (ucd.ie)
  • Work from the Weissmann lab has led to the development of new assays for prion replication and toxicity, as well as characterizing sources of infectivity in humans. (innovations-report.com)
  • Interestingly, the same protein is able to cause different infectious forms (or strains) of the disease in inbred hosts with the same genotype ( Bruce, 1996 ). (wiley.com)
  • 1999) 'Transgenetic investigations of the species barrier and prion strains' In: Prusiner, S. B (eds). (ucd.ie)
  • Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. (cdc.gov)
  • In this chapter, the cellular and molecular biology of prion proteins in general is discussed and prophylactic and therapeutic concepts derived thereof are introduced. (eurekaselect.com)
  • The molecular structure of the infectious agent is unknown but is referred to as a prion. (biology-online.org)
  • We examined polymorphism of prion protein open reading frame. (nii.ac.jp)
  • We immunohistochemically examined tissue sections from patients with prion protein polymorphism using hydrolytic autoclaving enhancement. (nii.ac.jp)
  • An assay comprises contacting cells containing a conformationally altered protein with test compound and determining if the altered protein is cleared. (google.com)
  • Another assay comprises contacting organ or tissue homogenate (at pH 5.0 or less) with test compound to determine if altered protein in the homogenate is cleared. (google.com)
  • Publications] Doh-ura K: 'Creutzfeldt-Jakob disease patients with Congophilic kuru plaques have the missense variant protein common to Gerstmann-Straussler syndrome. (nii.ac.jp)
  • Since the epidemic of 'mad cow disease' in the 1980s and 90s, and the emergence of its human equivalent, variant Creutzfeld-Jacob disease, there has been a great deal of research into prions, the causative agents. (scienceinschool.org)
  • The webmaster considered a SOD function for prion protein in great detail in a June 1998 web and listserve posting while working out the 3D structure of the repeat region , mainly motivated by binding of both copper and zinc and the helical repeat structure so suggestive of a redox function. (mad-cow.org)
  • There is now compelling evidence for human to human transmission through blood transfusions from presymptomatic carriers and experts are warning that the real epidemic may be yet to come. (biology-online.org)
  • A paradigm is proposed similar to that used for HIV screening but with unique features: compulsory testing of all blood/organ donors and individuals undergoing surgery or invasive procedures who have a significant risk of disease transmission. (biology-online.org)
  • There is, therefore, a need to ensure that regulatory authorities worldwide have reliable information to assess risk and evaluate product safety, so that steps can be taken to prevent the transmission of TSE to humans via biological and other pharmaceutical products. (who.int)
  • In this article the ethical implications of the availability of these tests are elaborated and comparisons drawn with predictive genetic testing for Huntington's disease and screening for HIV. (biology-online.org)
  • We are currently modeling a number of rare human genetic diseases in C. elegans . (nih.gov)
  • Genetic forms show a striking variability in their clinical and neuropathological picture and can sometimes mimic other neurodegenerative diseases. (biomedcentral.com)
  • To date, more than 50 different PRNP variants have been identified in large reference datasets of human genetic variations. (biomedcentral.com)
  • The Section on Physical Biochemistry is engaged in quantitative studies of effect of high concentrations of nominally inert small molecule and macromolecular cosolutes on the thermodynamic and hydrodynamic behavior of selected proteins and nucleic acids. (nih.gov)
  • The identification and characterization of such effects is essential for an understanding and quantitative prediction of the functional behavior of proteins and nucleic acids within complex physiological media. (nih.gov)
  • There is still a veil of mystery around prions and exactly how they replicate, cross the blood-brain barrier and cross the species barrier - i.e. infect different species of host. (scienceinschool.org)
  • H Schatzl and coworkers have posted partial prion sequences from new 7 species of bird. (mad-cow.org)
  • Deletions of a single unit are common polymormphisms both in humans and other species without a strong association with CJD. (mad-cow.org)
  • Compounds which are found to clear the altered protein are useful in preventing, arresting and/or reversing (i.e. treating) a disease associated with the conformationally altered protein. (google.com)