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Encyclopedia > Prion
Prion Diseases (TSEs)
Classification & external resources
ICD-10 A81
ICD-9 046

A prion (IPA: /ˈpriːɒn/[1]listen ) — short for proteinaceous infectious particle (-on by analogy to virion) — is a poorly-understood hypothetical infectious agent - that according to the "protein only" hypothesis is composed only of proteins.[2] Prions are thought to cause a number of diseases in a variety of mammals, including bovine spongiform encephalopathy (BSE aka "mad cow disease") in cattle and the Creutzfeldt-Jakob disease (CJD) in humans. All thus-far hypotheized prion diseases affect the structure of the brain or other neural tissue, and all are currently untreatable and thought to be fatal.[3] In general usage, prion can refer to both the theoretical unit of infection or the specific protein (e.g. PrP) that is thought to be the infective agent, whether or not it is in an infective state. Species Fairy Prion, Slender-billed Prion, Fulmar Prion, Broad-billed Prion, Antarctic Prion, Salvins Prion, A prion is a petrel (genus Pachyptila) found in Antarctica and nearby islands. ... In particle physics, preons are postulated point-like particles, conceived to be subcomponents of quarks and leptons. ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... Image File history File links Pronunciation_prion. ... A common alternate meaning of virus is computer virus. ... This false-colored electron micrograph shows a malaria sporozoite migrating through the midgut epithelia. ... A representation of the 3D structure of myoglobin showing coloured alpha helices. ... Subclasses & Infraclasses Subclass †Allotheria* Subclass Prototheria Subclass Theria Infraclass †Trituberculata Infraclass Metatheria Infraclass Eutheria Mammals (class Mammalia) are warm-blooded, vertebrate animals characterized by the presence of sweat glands, including milk producing sweat glands, and by the presence of: hair, three middle ear bones used in hearing, and a neocortex... Classic image of a cow with BSE. A notable feature of such disease is the inability (of the infected animal) to stand. ... Bovine spongiform encephalopathy (BSE or commonly mad cow disease) is a fatal, neurodegenerative disease of cattle, which infects by a mechanism that shocked biologists on its discovery in late 20th century and appears transmissible to humans. ... For general information about the genus, including other species of cattle, see Bos. ... Creutzfeldt-Jakob disease (CJD) is a very rare and incurable degenerative neurological disorder (brain disease) that is ultimately fatal. ... Human brain In animals, the brain (enkephale) (Greek for in the skull), is the control center of the central nervous system, responsible for behavior. ... Neurons (also called nerve cells) are the primary cells of the nervous system. ... Kochs postulates (or Henle-Koch postulates) are four criteria designed to establish a causal relationship between a causative microbe and a disease. ...


Prions are hypothesized to infect and propagate by refolding abnormally into a structure which is able to convert normal molecules of the protein into the abnormally structured form. All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. This altered structure is extremely stable and accumulates in infected tissue, causing cell death and tissue damage.[4] This stability means that prions are resistant to denaturation by chemical and physical agents, making disposal and containment of these particles difficult. Protein before and after folding. ... Proteins are an important class of biological macromolecules present in all biological organisms, made up of such elements as carbon, hydrogen, nitrogen, oxygen, and sulfur. ... 3D (left and center) and 2D (right) representations of the terpenoid molecule atisane. ... For other uses, see Amyloid (disambiguation). ... Diagram of β-pleated sheet with H-bonding between protein strands The β sheet (also β-pleated sheet) is the second form of regular secondary structure in proteins — the first is the alpha helix — consisting of beta strands connected laterally by three or more hydrogen bonds, forming a generally twisted, pleated sheet. ... Irreversible egg protein denaturation and loss of solubility, caused by the high temperature (while cooking it) Denaturation is the alteration of a protein or nucleic acids shape through some form of external stress (for example, by applying heat, acid or alkali), in such a way that it will no...


Proteins showing prion-type behavior are also found in some fungi and this has been quite important in helping to understand mammalian prions. However, fungal prions do not appear to cause disease in their hosts and may even confer an evolutionary advantage through a form of protein-based inheritance.[5] For the fictional character, see Fungus the Bogeyman. ... It has been suggested that this article or section be merged with PSI (prion). ... This article is about evolution in biology. ... See Heredity (disambiguation) for other meanings. ...

Contents

Discovery

The radiation biologist Tikvah Alper and the mathematician John Stanley Griffith developed the hypothesis during the 1960s that some transmissible spongiform encephalopathies are caused by an infectious agent consisting solely of proteins.[6][7] This theory was developed to explain the discovery that the mysterious infectious agent causing the diseases scrapie and Creutzfeldt-Jakob Disease resisted ultraviolet radiation (which does break down nucleic acids - present in viruses and all known living things), but yet responded to agents(?). The DNA discoverer Sir Francis Crick recognized the potential importance of the Griffith protein-only hypothesis for scrapie propagation in the second edition of his famous "Central dogma of molecular biology".[8] While asserting that the flow of sequence information from protein to protein, or from protein to RNA and DNA was "precluded" by this dogma, he noted that Griffith's hypothesis was a potential contradiction to this dogma (although it was not so promoted by Griffith). Since the revised "dogma" was formulated, in part, to accommodate the then-recent discovery of reverse transcription by Howard Temin and David Baltimore (who won the Nobel Prize in 1975), proof of the protein-only hypothesis might be seen as a "sure bet" for a future Nobel Prize. Transmissible spongiform encephalopathies (TSEs, also known as prion diseases) are a group of progressive conditions that affect the brain and nervous system of humans and animals and are transmitted by prions. ... A representation of the 3D structure of myoglobin showing coloured alpha helices. ... Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. ... Creutzfeldt-Jakob disease (CJD) is a very rare and incurable degenerative neurological disorder (brain disease) that is ultimately fatal. ... For other uses, see Ultraviolet (disambiguation). ... Look up nucleic acid in Wiktionary, the free dictionary. ... Francis Harry Compton Crick OM FRS (8 June 1916 – 28 July 2004), (Ph. ... Information flow in biological systems The central dogma of molecular biology was first enunciated by Francis Crick in 1958[1] and re-stated in a Nature paper published in 1970:[2] POSTLEWAITE IS A TOOL The central dogma of molecular biology deals with the detailed residue-by-residue transfer of... Reverse transcriptase is an enzyme used by all retroviruses and retrotransposons that transcribes the genetic information from the virus or retrotransposon from RNA into DNA, which can integrate into the host genome. ... David Baltimore (b. ...


Stanley B. Prusiner of the University of California, San Francisco announced in 1982 that his team had purified the hypothetical infectious prion, and that the infectious agent consisted mainly of a specific protein - though they did not manage to satisfactorily isolate the protein until two years after Prusiner's making his announcement.[9] Prusiner coined the word "prion" as a name for the infectious agent, by combining the first two syllables of the words proteinaceous and infectious.[10] While the infectious agent was named a prion, the specific protein that the prion was made of was named PrP, an abbreviation for "protease-resistant protein". Prusiner was awarded the Nobel Prize in Physiology or Medicine in 1997 for his research into prions.[11] Stanley Ben Prusiner (born May 28, 1942[1]) is an American neurologist and biochemist. ... UCSF in 1908, with the streetcar that used to run on Parnassus Avenue The University of California, San Francisco (UCSF) is one of the worlds leading centers of health sciences research, patient care, and education. ... A representation of the 3D structure of myoglobin showing coloured alpha helices. ... Emil Adolf von Behring was the first person to receive the Nobel Prize in Physiology or Medicine, for his work on the treatment of diphtheria. ...


Structure

Image File history File links Mergefrom. ... The mature form of PrPC is 253 amino acids long including two signal sequences in the amino- and carboxy- terminal ends which are removed during post-translational modification. ...

Isoforms

The protein that prions are made of is found throughout the body, even in healthy people and animals. However, the prion protein found in infectious material has a different structure and is resistant to proteases, the enzymes in the body that can normally break down proteins. The normal form of the protein is called PrPC, while the infectious form is called PrPSc — the C refers to 'cellular' or 'common' PrP, while the Sc refers to 'scrapie', a prion disease occurring in sheep.[12] While PrPC is structurally well-defined, PrPSc is certainly polydisperse and defined at a relatively poor level. PrP can be induced to fold into other more-or-less well-defined isoforms in vitro, and their relationship to the form(s) that are pathogenic in vivo is not yet clear. Peptidases (proteases [pronounced pro-tea-aces] and proteolytic enzymes are also commonly used) are enzymes which break peptide bonds of proteins. ... Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. ... A polydisperse polymer is one with a wide range of molecular masses. ...


PrPC

PrPC is a normal protein found on the membranes of cells. It has 209 amino acids (in humans), one disulfide bond, a molecular weight of 35-36kDa and a mainly alpha-helical structure. Several topological forms exist; one cell surface form anchored via glycolipid and two transmembrane forms.[13] Its function has not been fully resolved. PrPC binds copper (II) ions with high affinity..[14] The significance of this is not clear, but it presumably relates to PrP structure or function. PrPC is readily digested by proteinase K and can be liberated from the cell surface in vitro by the enzyme phosphoinositide phospholipase C (PI-PLC), which cleaves the glycophosphatidylinositol (GPI) glycolipid anchor.[15] Look up cell membrane in Wiktionary, the free dictionary. ... Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell being used to describe the smallest unit of a living organism Cells in culture, stained for keratin (red) and DNA (green) The cell is the... This article is about the class of chemicals. ... In chemistry, a disulfide bond is a single covalent bond derived from the coupling of thiol groups. ... Side view of an α-helix of alanine residues in atomic detail. ... In biochemistry, the membrane topology of an transmembrane protein describes which portions of the amino-acid sequence of the protein lie within the plane of the surrounding lipid bilayer and which portions protrude into the watery environment on either side. ... Glycolipids are carbohydrate-attached lipids. ... A transmembrane protein is a protein that spans the entire biological membrane. ... For other uses, see Copper (disambiguation). ... This article is about the electrically charged particle. ... Phospholipase C is a key enzyme in phosphatidylinositol (PIP2) metabolism and lipid signaling pathways. ... A GPI anchor or glycosylphosphatidylinositol is a common posttranslational modification of the C-terminus of membrane-attached proteins. ...


PrPSc

The infectious isoform of PrPC, known as PrPSc, is able to convert normal PrPC proteins into the infectious isoform by changing their conformation. Although the exact 3D structure of PrPSc is not known, there is increased β-sheet content in the diseased form of the molecule, replacing normal areas of α-helix.[16] Aggregations of these abnormal isoforms may form highly structured amyloid fibers. The end of a fiber acts as a template for the free protein molecules, causing the fiber to grow. Small differences in the amino acid sequence of prion-forming regions lead to distinct structural features on the surface of prion fibers. As a result, only free protein molecules that are identical in amino acid sequence to the prion protein can be recruited into the growing fiber. In biology, a protein isoform is a version of a protein with some small differences, usually a splice variant or the product of some posttranslational modification. ... Conformation generally means structural arrangement. ... Diagram of β-pleated sheet with H-bonding between protein strands The β sheet (also β-pleated sheet) is the second form of regular secondary structure in proteins — the first is the alpha helix — consisting of beta strands connected laterally by three or more hydrogen bonds, forming a generally twisted, pleated sheet. ... Side view of an α-helix of alanine residues in atomic detail. ... For other uses, see Amyloid (disambiguation). ...


Function

PrP and long-term memory

There is evidence that PrP may have a normal function in maintenance of long term memory.[17] Maglio and colleagues have shown that mice without the genes for normal cellular PrP protein have altered hippocampal LTP.[18] Long-term memory (LTM) is memory that lasts from days to years. ... For other uses, see Hippocampus (disambiguation). ... Long-term potentiation (LTP) is the persistent increase in synaptic strength following high-frequency stimulation of a chemical synapse. ...


== Prion disease ==http://en.wikipedia.org/skins-1.5/common/images/button_nowiki.png

Microscopic "holes" are characteristic in prion-affected tissue sections, causing the tissue to develop a "spongy" architecture

Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form plaques known as amyloids, which disrupt the normal tissue structure. This disruption is characterized by "holes" in the tissue with resultant spongy architecture due to the vacuole formation in the neurons.[19] Other histological changes include astrogliosis and the absence of an inflammatory reaction.[20] While the incubation period for prion diseases is generally quite long, once symptoms appear the disease progresses rapidly, leading to brain damage and death.[21] Neurodegenerative symptoms can include convulsions, dementia, ataxia (balance and coordination dysfunction), and behavioural or personality changes. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... Transmissible spongiform encephalopathies (TSEs, also known as prion diseases) are a group of progressive conditions that affect the brain and nervous system of humans and animals and are transmitted by prions. ... A diagram showing the CNS: 1. ... For other uses, see Amyloid (disambiguation). ... Biological tissue is a group of cells that perform a similar function. ... Schematic of typical animal cell, showing subcellular components. ... Astrocytosis (astrogliosis) is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons, typically because of hypoglycemia or oxygen deprivation (hypoxia). ... An abscess on the skin, showing the redness and swelling characteristic of inflammation. ... Incubation period, also called the latent period or latency period, is the time elapsed between exposure to a pathogenic organism, or chemical or radiation, and when symptoms and signs are first apparent. ... This article is about the medical condition. ... For other uses, see Dementia (disambiguation). ... For other uses, see Ataxia (disambiguation). ...


All known prion diseases, collectively called transmissible spongiform encephalopathies (TSEs), are untreatable and fatal.[22] However, a vaccine has been developed in mice that may provide insight into providing a vaccine in humans to resist prion infections.[23] Additionally, in 2006 scientists announced that they had genetically engineered cattle lacking a necessary gene for prion production - thus theoretically making them immune to BSE,[24] building on research indicating that mice lacking normally-occurring prion protein are resistant to infection by scrapie prion protein.[25]


Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very similar in all mammals.[26] Due to small differences in PrP between different species, it is unusual for a prion disease to be transmitted from one species to another. However, the human prion disease variant Creutzfeldt-Jakob disease is believed to be caused by a prion which typically infects cattle and is transmitted through infected meat.[27]


Some researchers have suggested that metal ion interactions with prion proteins might be relevant to the progression of prion-mediated disease, based on epidemiological studies of clusters of prion disease in locales with low soil concentrations of copper.[28]


The following diseases are believed to be caused by prions.

Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. ... Species See text. ... This article is about the domestic species. ... Classic image of a cow with BSE. A notable feature of such disease is the inability (of the infected animal) to stand. ... For general information about the genus, including other species of cattle, see Bos. ... Transmissible mink encephalopathy is caused by proteins called prions ... For other uses, see Mink (disambiguation). ... Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of deer and American elk (wapiti). ... For other uses, see Elk (disambiguation). ... Binomial name (Rafinesque, 1817) The mule deer (Odocoileus hemionus) is a deer whose habitat is in the western half of North America. ... Feline spongiform encephalopathy is caused by protiens called prions ... Binomial name Felis catus Linnaeus, 1758 Synonyms Felis lybica invalid junior synonym The cat (or domestic cat, house cat) is a small carnivorous mammal. ... Binomial name Tragelaphus angasii Gray, 1849 Male nyala. ... Species Oryx beisa Rüppell, 1835 Oryx dammah Cretzschmar, 1827 Oryx gazella (Linnaeus, 1758) Oryx leucoryx Pallas, 1766 An Oryx is one of three or four large antelope species of the genus Oryx, typically having long straight almost upright or swept back horns. ... This article does not adequately cite its references or sources. ... Binomial name Linnaeus, 1758 The present-day distribution of Ostriches. ... Creutzfeldt-Jakob disease (CJD) is a very rare and incurable degenerative neurological disorder (brain disease) that is ultimately fatal. ... Ancient Greek painting in a vase, showing a physician (iatros) bleeding a patient. ... Gerstmann-Sträussler-Scheinker syndrome (GSS) is a very rare, usually familial, neurodegenerative disease that affects patients in the third to seventh decades of life. ... Fatal familial insomnia (FFI) is a very rare autosomal dominant inherited disease of the brain. ... Kuru (also known as laughing sickness due to the outbursts of laughter that mark its second phase) was first noted in New Guinea in the early 1900s. ...

Transmission

Proposed mechanism of prion propagation

Although the identity and general properties of prions are now well understood, the mechanism of prion infection and propagation remains mysterious. It is often assumed that the diseased form directly interacts with the normal form to make it rearrange its structure. One idea, the "Protein X" hypothesis, is that an as-yet unidentified cellular protein (Protein X) enables the conversion of PrPC to PrPSc by bringing a molecule of each of the two together into a complex.[32] Image File history File links Download high resolution version (879x766, 31 KB) Summary Author of diagram: purple, released to public domain Licensing I, the creator of this work, hereby release it into the public domain. ... Image File history File links Download high resolution version (879x766, 31 KB) Summary Author of diagram: purple, released to public domain Licensing I, the creator of this work, hereby release it into the public domain. ...


Current research suggests that the primary method of infection in animals is through ingestion. It is thought that prions may be deposited in the environment through the remains of dead animals and via urine, saliva, and other body fluids. They may then, Chappell R, McKenzie D, Aiken J |title=Oral Transmissibility of Prion Disease is Enhanced by Binding to Soil Particles |journal=PLoS Pathogens |volume=3 |issue=7 |year=2007 |pmid=17616973 |doi=10.1371/journal.ppat.0030093}}</ref>


Sterilization

Infectious particles possessing nucleic acid are dependent upon it to direct their continued replication. Prions however, are infectious by their effect on normal versions of the protein. Therefore, sterilizing prions involves the denaturation of the protein to a state where the molecule is no longer able to induce the abnormal folding of normal proteins. However, prions are generally quite resistant to denaturation by proteases, heat, radiation, and formalin treatments,[33] although their infectivity can be reduced by such treatments. Irreversible egg protein denaturation and loss of solubility, caused by the high temperature (while cooking it) Denaturation is the alteration of a protein or nucleic acids shape through some form of external stress (for example, by applying heat, acid or alkali), in such a way that it will no... Proteases (proteinases, peptidases, or proteolytic enzymes) are enzymes that break peptide bonds between amino acids of proteins. ... For other uses, see Heat (disambiguation) In physics, heat, symbolized by Q, is energy transferred from one body or system to another due to a difference in temperature. ... For other uses, see Radiation (disambiguation). ... The chemical compound formaldehyde (also known by IUPAC nomenclature as methanal), is a gas with a strong pungent smell. ...


Prions can be denatured by subjecting them to a temperatures of 134 degrees Celsius (274 degrees Fahrenheit) for 18 minutes in a pressurised steam autoclave.[34] Ozone sterilization is currently being studied as a potential method for prion deactivation.[35] Renaturation of a completely denatured prion to infectious status has not yet been achieved, however partially denatured prions can be renatured to an infective status under certain artificial conditions.[36] Front loading autoclaves are common Stovetop autoclaves need to be monitored carefully and are the simplest of all autoclaves Multiple large autoclaves are used for processing substantial quantities of laboratory equipment prior to reuse, and infectious material prior to disposal. ...


The World Health Organisation recommends the following procedure for the sterilization of all heat-resistant surgical instruments that are potentially contaminated with prions: For other meanings of the acronym WHO, see WHO (disambiguation) WHO flag Headquartered in Geneva, Switzerland, the World Health Organization (WHO) is an agency of the United Nations, acting as a coordinating authority on international public health. ...


(1) Immerse in a pan containing 1N NaOH and heat in a gravity-displacement autoclave at 121°C for 30 min; clean; rinse in water; and then subject to routine sterilization. For other uses, see Concentration (disambiguation). ...


(2) Immerse in 1N NaOH or sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; transfer instruments to water; heat in a gravity-displacement autoclave at 121°C for 1 hour; clean; and then subject to routine sterilization


(3) Immerse in 1N NaOH or sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; remove and rinse in water, then transfer to an open pan and heat in a gravity-displacement (121°C) or in a porous-load (134°C) autoclave for 1 hour; clean; and then subject to routine sterilization [37]'



Sterilization & Decomposition of Organic Materials


One method that will decompose any organic material to its basic constituents uses cold (non-equilibrium) oxygen ion plasmas. [This coverts the organic materials into carbon dioxide, water, nitrogen gas, nitrogen oxides, phosphorous oxides, sulfur dioxide, etc.] Even basal graphite can be converted to carbon dioxide using this method. Another way uses chromerge (Cr2O6) in concentrated sulfuric acid. This is a common method to clean glassware used in organic and analytical chemistry.


Another method for decomposing and disposing of any organic compound it burning it at high temperatures in an oxygen-rich atmosphere. This method is used for the disposal of deadly chemical weapons such as nerve gasses and mustard gas. This reduces it all to simple gaseous compounds, including water vapor, that are safe to release into the environment. Early detection of chemical agents Sociopolitical climate of chemical warfare While the study of chemicals and their military uses was widespread in China, the use of toxic materials has historically been viewed with mixed emotions and some disdain in the West (especially when the enemy were doing it). ...


Debate

Protein-only hypothesis

Prior to the discovery of prions, it was thought that all pathogens used nucleic acids to direct their replication. The "protein-only hypothesis" states that a protein structure can replicate without the use of nucleic acid. This was initially controversial as it contradicts the so-called "central dogma of molecular biology," which describes nucleic acid as the central form of replicative information. A pathogen (from Greek pathos, suffering/emotion, and gene, to give birth to), infectious agent, or more commonly germ, is a biological agent that causes disease or illness to its host. ... Look up nucleic acid in Wiktionary, the free dictionary. ... Information flow in biological systems The central dogma of molecular biology was first enunciated by Francis Crick in 1958[1] and re-stated in a Nature paper published in 1970:[2] POSTLEWAITE IS A TOOL The central dogma of molecular biology deals with the detailed residue-by-residue transfer of...


Evidence in favor of a protein-only hypothesis include:[38]

  • No virus particles, bacteria, or fungi have been conclusively associated with prion diseases
  • No nucleic acid has been conclusively associated with infectivity; agent is resistant to degradation by nucleases
  • No immune response to infection
  • PrPSc experimentally transmitted between one species and another results in PrPSc with the amino-acid sequence of the recipient species, suggesting that replication of the donor agent does not occur
  • Level of infectivity is associated with levels of PrPSc
  • PrPSc and PrPC do not differ in amino-acid sequence, therefore a PrPSc-specific nucleic acid is a redundant concept
  • Familial prion disease occurs in families with a mutation in the PrP gene, and mice with PrP mutations develop prion disease despite controlled conditions where transmission is prevented

A nuclease is an enzyme capable of cleaving the phosphodiester bonds between the nucleotide subunits of nucleic acids. ...

Multi-component hypothesis

In 2007, biochemist Surachai Supattapone and his colleagues at Dartmouth College produced purified infectious prions de novo from defined components (PrPC, co-purified lipids, and a synthetic polyanionic molecule) [39]. These researchers also showed that the polyanionic molecule required for prion formation was selectively incorporated into high-affinity complexes with PrP molecules, leading them to hypothesize that infectious prions may be composed of multiple host components, including PrP, lipid, and polyanionic molecules, rather than PrPSc alone [40]. Dartmouth College is a private, coeducational university located in Hanover, New Hampshire, USA. Incorporated as Trustees of Dartmouth College,[6][7] it is a member of the Ivy League and one of the nine colonial colleges founded before the American Revolution. ...


Viral hypothesis

The protein-only hypothesis was initially met with skepticism and still has critics. For more than a decade, Yale University neuropathologist Laura Manuelidis has been proposing that prion diseases are caused instead by an unidentifiable "slow virus". In January 2007 she and her colleagues published an article in the Proceedings of the National Academy of Science reporting to have found the virus in 10%, or less, of their scrapie-infected cells in culture.[41][42] Yale redirects here. ... Laura Manuelidis is a physician and neuropathologist at Yale University. ... The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences. ... This article is about biological infectious particles. ...


The Virion Hypothesis states that TSEs are caused by a replicable informational molecule (which is likely to be a nucleic acid) bound to PrP. Many TSEs, including Scrapie and BSE, show strains with specific and distinct biological properties, a feature which supporters of the Virion hypothesis feel is not explained by prions. The presence of a nucleic acid bound to the protein would explain the strains observed. It has also been shown that TSEs including BSE retain their host-specific properties after passage through many different species. [43]


Evidence in favor of a viral hypothesis include:[38]

  • No bacteria or other living organisms have been found in prion-affected organisms, defaulting to the idea that a virus must be involved
  • The long incubation and rapid onset of symptoms resembles some viral infections, such as HIV-induced AIDS
  • Differences in prion infectivity, incubation, symptomology and progression among species resembles the "strain variation" seen between viruses, especially RNA viruses

Species Human immunodeficiency virus 1 Human immunodeficiency virus 2 Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS, a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections). ... For other uses, see AIDS (disambiguation). ... An RNA virus is a virus that either uses RNA as its genetic material, or whose genetic material passes through an RNA intermediate during replication. ...

Heavy metal poisoning hypothesis

Mark Purdey and Dr. David R. Brown have suggested that PrPC is an anti-oxidant molecule when bound to copper ions and that loss of this activity could cause disease. They have hypothesised that abnormal amounts of copper and manganese in the environment or animal feed could precipitate this.[44]


Genetics

A gene for the normal protein has been isolated: the PRNP gene.[45] Some prion diseases can be inherited, and in all inherited cases there is a mutation in the PRNP gene. Many different PRNP mutations have been identified and it is thought that the mutations somehow make PrPC more likely to spontaneously change into the abnormal PrPSc form. Prion diseases are the only known diseases that can be sporadic, genetic, or infectious. For other uses, see Gene (disambiguation). ... PRNP (PRioN Protein (Creutzfeld-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia)) is a gene that provides instructions to make a protein called the prion protein (PrP), which is active in the brain and several other tissues. ... For linguistic mutation, see Apophony. ... A genetic disorder, or genetic disease is a disease caused, at least in part, by the genes of the person with the disease. ... This false-colored electron micrograph shows a malaria sporozoite migrating through the midgut epithelia. ...


Prions in yeast and other fungi

Prion-like proteins that behave in a similar way to PrP are found naturally in some fungi and non-mammalian animals. A group at the Whitehead Institute has argued that some of the fungal prions are not associated with any disease state and may have a useful role; however, researchers at the NIH have also provided strong arguments demonstrating that fungal prions should be considered a diseased state. Research into fungal prions has given strong support to the protein-only hypothesis for mammalian prions, since it has been demonstrated that purified protein extracted from cells with the prion state can convert the normal form of the protein into the infectious form in vitro, and in the process, preserve the information corresponding to different strains of the prion state. It has also shed some light on prion domains, which are regions in a protein that promote the conversion. Fungal prions have helped to suggest mechanisms of conversion that may apply to all prions. Founded in 1984, the Whitehead Institute for Biomedical Research is a non-profit research and teaching institution located in Cambridge, Massachusetts. ... In vitro (Latin: within the glass) refers to the technique of performing a given experiment in a test tube, or, generally, in a controlled environment outside a living organism. ...


See also


Image File history File links Wikibooks-logo-en. ... Protein before and after folding. ... Proteopathy (Proteo- [pref. ... In biochemistry and chemistry, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates. ... Transmissible spongiform encephalopathies (TSEs, also known as prion diseases) are a group of progressive conditions that affect the brain and nervous system of humans and animals and are transmitted by prions. ...


Further Reading

Deadly Feasts: The "Prion" Controversy and the Public's Health[46], by Richard Rhodes offers a history of research into Kuru, CJD, Mad Cow Disease, Scrapie and related disorders through 1998. The Touchstone paperback edition includes an Afterword that reviews the viral and virion hypotheses. Deadly Feasts extensively covers public policy debates on food safety standards. The Pathological Protein: Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases covers the science of TSE diseases in greater depth than Deadly Feasts but is not so thorough on policy issues.[47] Richard Rhodes (born July 4, 1937) is an American author of fiction and verity, including the Pulitzer Prize-winning The Making of the Atomic Bomb in 1986, and most recently, John James Audubon: the Making of an American in 2004. ...


References

  1. ^ "Prion". Oxford English Dictionary. Oxford University Press. 2nd ed. 1989.
  2. ^ http://www.pnas.org/cgi/content/extract/105/1/11?etoc
  3. ^ Prusiner SB (1998). "Prions". Proc. Natl. Acad. Sci. USA 95 (23): 13363-83. doi:10.1073/pnas.95.23.13363. PMID 9811807. 
  4. ^ Dobson CM (2001). "The structural basis of protein folding and its links with human disease". Philos Trans R Soc Lond B Biol Sci 356 (1406): 133-145. doi:10.1098/rstb.2000.0758. PMID 11260793. 
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A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Gary Taubes is a science writer. ... Stanley B. Prusiner, M.D., a Professor of Neurology and Biochemistry at the University of California, San Francisco, was awarded the Nobel Prize in physiology or medicine in 1997 for his discovery of prions a class of infectious self-reproducing agents composed of protein. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 131st day of the year (132nd in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 16th day of the year in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 133rd day of the year (134th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2005 (MMV) was a common year starting on Saturday (link displays full calendar) of the Gregorian calendar. ... May 14 is the 134th day of the year (135th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 128th day of the year (129th in leap years) in the Gregorian calendar. ... ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 1st day of the year in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 1st day of the year in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 270th day of the year (271st in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 270th day of the year (271st in leap years) in the Gregorian calendar. ... This article is about the year. ... is the 148th day of the year (149th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 270th day of the year (271st in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... is the 33rd day of the year in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 33rd day of the year in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

External links

The International Committee on Taxonomy of Viruses (ICTV) is a committee which authorises and organises the taxonomic classification of viruses. ... Ó GloFish: the first genetically modified animal to be sold as a pet. ... // A00-A79 - Bacterial infections, and other intestinal infectious diseases, and STDs (A00-A09) Intestinal infectious diseases (A00) Cholera (A01) Typhoid and paratyphoid fevers (A010) Typhoid fever (A02) Other Salmonella infections (A03) Shigellosis (A04) Other bacterial intestinal infections (A040) Enteropathogenic Escherichia coli infection (A045) Campylobacter enteritis (A046) Enteritis due to Yersinia... Creutzfeldt-Jakob disease (CJD) is a very rare and incurable degenerative neurological disorder (brain disease) that is ultimately fatal. ... Kuru (also known as laughing sickness due to the outbursts of laughter that mark its second phase) was first noted in New Guinea in the early 1900s. ... Gerstmann-Sträussler-Scheinker syndrome (GSS) is a very rare, usually familial, neurodegenerative disease that affects patients in the third to seventh decades of life. ... Fatal familial insomnia (FFI) is a very rare autosomal dominant inherited disease of the brain. ... Classic image of a cow with BSE. A notable feature of such disease is the inability (of the infected animal) to stand. ... Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. ... Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of deer and American elk (wapiti). ... Transmissible mink encephalopathy is caused by proteins called prions ...

  Results from FactBites:
 
Prion - Wikipedia, the free encyclopedia (1358 words)
Prions are abnormally-structured forms of a species-specific host cell surface protein, which are able to convert normal molecules of the protein into the abnormal structure.
Prusiner coined the word "prion" as a name for the infectious agent, by combining the first two syllables of the words "proteinaceous" and "infectious." While the infectious agent was named a prion, the specific protein that the prion was made of was named PrP, an abbreviation for "prion-related protein".
The prion hypothesis was highly controversial, because it seemed to contradict the so-called "central dogma of modern biology" that asserts all living organisms use nucleic acids to reproduce.
Prion - definition of Prion in Encyclopedia (1671 words)
Prions were first hypothesized in 1982 by Stanley B. Prusiner of UCSF, who was awarded the Nobel Prize in physiology or medicine in 1997 for the discovery.
Note that not all encephalopathies are caused by prions, as in the cases of PML (caused by the JC virus), CADASIL (caused by abnormal NOTCH3 protein activity), and Krabbe disease (caused by a deficiency of the enzyme galactosylceramidase).
Prion Diseases and the BSE Crisis (http://www.sciencemag.org/feature/data/prusiner/245.shl) (1997).
  More results at FactBites »

 
 

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