Citizendia

For the bird, see Prion (bird). The prions are small Petrels in the Genus Pachyptila. Together with the Blue Petrel, they form one of the four groups within the Procellariidae For the theoretical subatomic particle, see Preon. In Particle physics, preons are postulated "point-like" particles conceived to be subcomponents of Quarks and Leptons The word was coined
Prion Diseases (TSEs)
Classification and external resources
ICD-10A81
ICD-9046

A prion (IPA: /ˈpriːɒn/[1]listen (help·info)) — combination of the first two syllables of the words proteinaceous and infectious (-on by analogy to virion)[2] — is a poorly-understood hypothetical infectious agent that, according to the "protein only" hypothesis, is composed entirely of proteins. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. An infectious disease is a clinically evident Disease resulting from the presence of Pathogenic microbial agents including Pathogenic viruses Pathogenic Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl [3] Prions are thought to cause a number of diseases in a variety of mammals, including bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cattle and Creutzfeldt-Jakob disease (CJD) in humans. Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands Bovine Spongiform Encephalopathy ( BSE) commonly known as Mad-Cow Disease ( MCD) is a fatal Neurodegenerative disease in Cattle Cattle, colloquially referred to as cows, are domesticated Ungulates a member of the Subfamily Bovinae of the family Creutzfeldt-Jakob disease ( CJD) is a very rare and incurable degenerative neurological disorder ( Brain Disease) that is ultimately All thus-far hypothesized prion diseases affect the structure of the brain or other neural tissue, and all are currently untreatable and thought to be fatal. The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information [4] In general usage, prion can refer to both the theoretical unit of infection or the specific protein (e. Koch's postulates are four criteria designed to establish a causal relationship between a causative Microbe and a Disease. g. PrP) that is thought to be the infective agent, whether or not it is in an infective state.

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. Protein folding is the physical process by which a Polypeptide folds into its characteristic and functional three-dimensional structure. Proteins are an important class of biological Macromolecules present in all biological organisms made up of such elements as Carbon, Hydrogen In Chemistry, a molecule is defined as a sufficiently stable electrically neutral group of at least two Atoms in a definite arrangement held together by All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. Amyloids are insoluble fibrous Protein aggregates sharing specific structural traits The β sheet (also β-pleated sheet) is the second form of regular Secondary structure in Proteins consisting of beta strands connected laterally This altered structure is extremely stable and accumulates in infected tissue, causing cell death and tissue damage. [5] This stability means that prions are resistant to denaturation by chemical and physical agents, making disposal and containment of these particles difficult. Denaturation is a process in which Proteins or Nucleic acids lose their structure (tertiary structure by application of some external stress or compound for

Proteins showing prion-type behavior are also found in some fungi and this has been quite important in helping to understand mammalian prions. A fungus (ˈfʌŋgəs is a eukaryotic Organism that is a member of the kingdom Fungi (ˈfʌndʒaɪ 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. Fungal Prions have been investigated leading to a deeper understanding of disease-forming Mammalian prions eVolution is the third Album by eLDee, it was due to be released in 2008 [6]

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. Transmissible spongiform encephalopathies' ( TSEs, also known as prion diseases) are a group of progressive conditions that affect the Brain and Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl [7][8] 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 breaks down the nucleic acids that are present in viruses and all known living things). Scrapie is a fatal degenerative Disease that affects the Nervous systems of Sheep and Goats It is one of several Transmissible spongiform Creutzfeldt-Jakob disease ( CJD) is a very rare and incurable degenerative neurological disorder ( Brain Disease) that is ultimately Ultraviolet ( UV) light is Electromagnetic radiation with a Wavelength shorter than that of Visible light, but longer than X-rays A nucleic acid is a Macromolecule composed of chains of monomeric Nucleotides In Biochemistry these Molecules carry Genetic information 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". Francis Harry Compton Crick OM FRS (8 June 1916 – 28 July 2004 Ph The central dogma of molecular biology was first enunciated by Francis Crick in 1958 and re-stated in a Nature paper published in 1970 [9] 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. Reverse transcription is the process of making a double stranded DNA (deoxyribonucleic acid molecule from a single stranded RNA (ribonucleic acid template Howard Martin Temin ( December 10, 1934 &ndash February 9, 1994) was a U David Baltimore (born March 7, 1938) is an American biologist

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 announcement. Stanley Ben Prusiner (born May 28, 1942 In this work he coined the term prion, which comes from "proteinaceous infectious particle that lacks The University of California San Francisco ( UCSF) is one of the world's leading centers of Health sciences research Patient care, and education Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl [10] Prusiner coined the word "prion" as a name for the infectious agent, by combining the first two syllables of the words proteinaceous and infectious (-on by analogy to virion). [2] While the infectious agent was named a prion, the specific protein that the prion was made of was named PrP, an abbreviation for "prion protein". Prusiner was awarded the Nobel Prize in Physiology or Medicine in 1997 for his research into prions. The Nobel Prize in Physiology or Medicine (Nobelpriset i fysiologi eller medicin is awarded once a year by the Swedish Karolinska Institute. [11]

Structure

See also: PrP structure

Isoforms

The protein that prions are made of is found throughout the body, even in healthy people and animals. Isoforms Normal PrPC structure The normal PrP structure is 253 Amino acids long However, the prion protein found in infectious material has a different folding pattern and is resistant to proteases, the enzymes in the body that can normally break down proteins. A protease is any Enzyme that conducts Proteolysis, that is begins protein Catabolism by Hydrolysis of the Peptide bonds that link 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. Scrapie is a fatal degenerative Disease that affects the Nervous systems of Sheep and Goats It is one of several Transmissible spongiform [12] While PrPC is structurally well-defined, PrPSc is certainly polydisperse and defined at a relatively poor level. In Organic chemistry, the polydispersity index ( PDI) is a measure of the distribution of Molecular mass in a given Polymer sample 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.

PrPC

PrPC is a normal protein found on the membranes of cells. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called It has 209 amino acids (in humans), one disulfide bond, a molecular weight of 35-36kDa and a mainly alpha-helical structure. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this In Chemistry, a disulfide bond is a single Covalent bond derived from the coupling of Thiol groups A common motif in the Secondary structure of Proteins the alpha helix (α-helix is a right-handed coiled conformation resembling a spring, in which Several topological forms exist; one cell surface form anchored via glycolipid and two transmembrane forms. In Biochemistry, the membrane topology of an Transmembrane protein describes which portions of the amino-acid sequence of the protein lie within the plane Glycolipids are Carbohydrate -attached Lipids. Their role is to provide Energy and also serve as markers for cellular recognition A transmembrane protein is a Protein that spans the entire Biological membrane. [13] Its function has not been fully resolved. PrPC binds copper (II) ions with high affinity. Copper (ˈkɒpɚ is a Chemical element with the symbol Cu (cuprum and Atomic number 29 An ion is an Atom or Molecule which has lost or gained one or more Valence electrons giving it a positive or negative electrical charge [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. Proteinase K (also protease K or endopeptidase K) is a broad-spectrum Serine protease. Phospholipase C is a class of Enzymes that cleave Phospholipids just before the Phosphate group (see Figure Glycosylphosphatidylinositol ( GPI anchor) is a Glycolipid that can be attached to the C-terminus of a Protein during Posttranslational [15]

PrPSc

The infectious isoform of PrPC, known as PrPSc, is able to convert normal PrPC proteins into the infectious isoform by changing their conformation. A protein isoform is a version of a Protein with only small differences to another isoform of the same protein 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. The β sheet (also β-pleated sheet) is the second form of regular Secondary structure in Proteins consisting of beta strands connected laterally A common motif in the Secondary structure of Proteins the alpha helix (α-helix is a right-handed coiled conformation resembling a spring, in which [16] Aggregations of these abnormal isoforms may form highly structured amyloid fibers. Amyloids are insoluble fibrous Protein aggregates sharing specific structural traits 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.

Function

It has now been conclusively proven that the prion protein's normal cellular role is as a copper dependent antioxidant. An antioxidant is a Molecule capable of slowing or preventing the oxidation of other molecules [17] While a small number of researchers in the field pursue other possibilities, the majority of evidence from many researcher supports this finding.

PrP and long-term memory

There is evidence that PrP may have a normal function in maintenance of long term memory. Long-term memory ( LTM) is Memory that can last as little as a few days or as long as decades [18] Maglio and colleagues have shown that mice without the genes for normal cellular PrP protein have altered hippocampal LTP. The hippocampus is a part of the Forebrain, located in the medial Temporal lobe. In Neuroscience, long-term potentiation ( LTP) is the long-lasting improvement in communication between two Neurons that results from stimulating them [19]

PrP and stem cell renewal

A 2006 article from the Whitehead Institute for Biomedical Research indicates that PrP expression on stem cells is necessary for an organism's self-renewal of bone marrow. Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of The study showed that all long-term hematopoietic stem cells expressed PrP on their cell membrane and that hematopoietic tissues with such PrP-null stem cells exhibited increased sensitivity to cell depletion. Hematopoietic stem cells (HSCs are Stem cells that give rise to all the blood cell types including Myeloid ( Monocytes and Macrophages, Neutrophils [20]

Prion disease

Microscopic "holes" are characteristic in prion-affected tissue sections, causing the tissue to develop a "spongy" architecture.
Microscopic "holes" are characteristic in prion-affected tissue sections, causing the tissue to develop a "spongy" architecture.
Main article: Transmissible spongiform encephalopathy

Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form plaques known as amyloids, which disrupt the normal tissue structure. Transmissible spongiform encephalopathies' ( TSEs, also known as prion diseases) are a group of progressive conditions that affect the Brain and In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. Amyloids are insoluble fibrous Protein aggregates sharing specific structural traits Tissue is a cellular organizational level intermediate between cells and a complete organism This disruption is characterized by "holes" in the tissue with resultant spongy architecture due to the vacuole formation in the neurons. In general vacuole functions include Removing unwanted structural debris Isolating materials that might be harmful or a threat to the cell Containing [21] Other histological changes include astrogliosis and the absence of an inflammatory reaction. Astrocytosis ( astrogliosis) is an abnormal increase in the number of Astrocytes due to the destruction of nearby Neurons, typically because of Hypoglycemia Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens [22] While the incubation period for prion diseases is generally quite long, once symptoms appear the disease progresses rapidly, leading to brain damage and death. Incubation period is the Time elapsed between exposure to a Pathogenic Organism, or Chemical or radiation, and when Symptoms [23] Neurodegenerative symptoms can include convulsions, dementia, ataxia (balance and coordination dysfunction), and behavioural or personality changes. An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline Ataxia (from Greek α- as a negative prefix + -τάξις, meaning "lack of order" is a neurological sign and symptom consisting

All known prion diseases, collectively called transmissible spongiform encephalopathies (TSEs), are untreatable and fatal. [24] However, a vaccine has been developed in mice that may provide insight into providing a vaccine in humans to resist prion infections. [25] 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,[26] building on research indicating that mice lacking normally-occurring prion protein are resistant to infection by scrapie prion protein. [27]

Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very similar in all mammals. [28] 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. [29]

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. [30]

The following diseases are believed to be caused by prions.

Transmission

Proposed mechanism of prion propagation.
Proposed mechanism of prion propagation. Scrapie is a fatal degenerative Disease that affects the Nervous systems of Sheep and Goats It is one of several Transmissible spongiform The domestic goat ( Capra aegagrus hircus) is a subspecies of goat Domesticated from the Wild goat of Southwest Asia and Eastern Europe Bovine Spongiform Encephalopathy ( BSE) commonly known as Mad-Cow Disease ( MCD) is a fatal Neurodegenerative disease in Cattle Cattle, colloquially referred to as cows, are domesticated Ungulates a member of the Subfamily Bovinae of the family Transmissible mink encephalopathy (TME is rare Sporadic Disease that affects the Central nervous system of ranch-raised Mink. There are two living species of " mink," the American Mink and the European Mink. Chronic wasting disease (CWD is a Transmissible spongiform encephalopathy (TSE of Deer, Elk (wapiti and Moose. The elk, or wapiti ( Cervus canadensis) is one of the largest Species of Deer in the world and one of the largest Mammals in The mule deer ( Odocoileus hemionus) is a Deer whose habitat is in the western half of North America. Feline spongiform encephalopathy is a disease that affects the brains and livers of felines It is caused by Proteins called Prions Disease WikipediaManual of Style (spelling, articles should conform to one overall spelling style of English typically the one most linked to the article topic (if it is geographic The Nyala ( Tragelaphus angasii) is a South African Antelope. ORYX is an encryption algorithm used in cellular communications The Greater Kudu ( Tragelaphus strepsiceros) is a Woodland Antelope found throughout eastern and southern Africa. The Ostrich ( Struthio camelus) is a large Flightless bird native to Africa (and formerly the Middle East) Creutzfeldt-Jakob disease ( CJD) is a very rare and incurable degenerative neurological disorder ( Brain Disease) that is ultimately The terms iatrogenesis and iatrogenic artifact refer to adverse effects or complications caused by or resulting from medical treatment or advice Gerstmann-Sträussler-Scheinker syndrome (GSS is a very rare usually familial fatal neurodegenerative Disease that affects patients from 20 to 60 years in age Fatal familial insomnia (FFI is a very rare autosomal dominant inherited Prion Disease of the Brain. Kuru is a disease which affects the Brain. It was endemic among the Fore tribe of Papua New Guinea and was universally fatal

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. [34]

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 linger in the soil by binding to clay and other minerals. [35]

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. Denaturation is a process in which Proteins or Nucleic acids lose their structure (tertiary structure by application of some external stress or compound for However, prions are generally quite resistant to denaturation by proteases, heat, radiation, and formalin treatments,[36] although their infectivity can be reduced by such treatments. A protease is any Enzyme that conducts Proteolysis, that is begins protein Catabolism by Hydrolysis of the Peptide bonds that link In Physics, heat, symbolized by Q, is Energy transferred from one body or system to another due to a difference in Temperature Radiation, as in Physics, is Energy in the form of waves or moving Subatomic particles emitted by an atom or other body as it changes from a higher energy Formaldehyde is a Chemical compound with the formula H2CO It is the simplest Aldehyde —an organic compound containing a terminal Carbonyl

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. An autoclave is a pressurized device designed to heat aqueous solutions above their Boiling point at normal atmospheric pressure to achieve sterilization [37] Ozone sterilization is currently being studied as a potential method for prion deactivation. [38] 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. [39]

The World Health Organization recommends the following procedure for the sterilization of all heat-resistant surgical instruments that are potentially contaminated with prions:

(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. In Chemistry, concentration is the measure of how much of a given substance there is mixed with another substance

(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 [40]'

One method that will decompose any organic material to its basic constituents uses cold (non-equilibrium) oxygen ion plasmas. [This converts 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 is 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. Chemical warfare involves using the toxic properties of Chemical substances to kill injure or incapacitate an enemy. This reduces it all to simple gaseous compounds, including water vapor, that are safe to release into the environment.

Debate

Protein-only hypothesis

Prior to the discovery of prions, it was thought that all pathogens used nucleic acids to direct their replication. A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious A nucleic acid is a Macromolecule composed of chains of monomeric Nucleotides In Biochemistry these Molecules carry Genetic information 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. The central dogma of molecular biology was first enunciated by Francis Crick in 1958 and re-stated in a Nature paper published in 1970

Evidence in favor of a protein-only hypothesis include:[41]

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) [42]. A nuclease is an Enzyme capable of cleaving the Phosphodiester bonds between the nucleotide subunits of Nucleic acids Older papers may use terms such as Dartmouth College ( is a private, Coeducational University located in Hanover, New Hampshire, U 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 [43].

Viral hypothesis

The protein-only hypothesis has been criticised by those who feel that the simplest explanation of the evidence to date[44] is viral. For more than a decade, Yale University neuropathologist Laura Manuelidis has been proposing that prion diseases are caused instead by an unidentified "slow" virus. Laura Manuelidis is a Physician and neuropathologist at Yale University. 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. 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 A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable [45][46]

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. [47]

Evidence in favor of a viral hypothesis include:[41]

Genetics

A gene for the normal protein has been isolated: the PRNP gene. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance PRNP ( PRioN Protein (Creutzfeld-Jakob disease Gerstmann-Sträussler-Scheinker syndrome fatal familial insomnia) is a Gene that provides instructions to make a [48] Some prion diseases can be inherited, and in all inherited cases there is a mutation in the PRNP gene. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism 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. While these mutations can occur throughout the gene encoding the prion protein the most notable code for the five octopeptide repeats found near the signal peptide of the protein, e. g. if the number of octopeptide repeats is incresaed to thirteen it can result in Gerstmann-Straussler Syndrome(GSS). Other mutations that have previously identified as a possible cause of genetically induced prion diseases occur at positions 102, 117 & 198 (GSS), 178, 200, 210 & 232 (CJD) and 178 Fatal Familial Insomnia (FFI). Prion diseases are the only known diseases that can be sporadic, genetic, or infectious. A genetic disorder is a condition caused by abnormalities in Genes or Chromosomes While some diseases such as Cancer, are due to genetic abnormalities acquired An infectious disease is a clinically evident Disease resulting from the presence of Pathogenic microbial agents including Pathogenic viruses Pathogenic

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. Susan Lindquist's 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. Susan Lindquist (born 5 June 1949) is a well-known molecular biologist studying (among other things the biology of Protein folding, Heat-shock Founded in 1982, the Whitehead Institute for Biomedical Research is a non-profit research and teaching institution located in Cambridge Massachusetts. 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. In vitro ( Latin: within the glass refers to the technique of performing a given experiment in a controlled environment outside of a living Organism 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.

See also


Further reading

Deadly Feasts: The "Prion" Controversy and the Public's Health[49], by Richard Rhodes offers a history of research into Kuru, CJD, Mad Cow Disease, Scrapie and related disorders through 1998. Protein folding is the physical process by which a Polypeptide folds into its characteristic and functional three-dimensional structure. Proteopathy (Proteo- protein -pathy disease proteopathies pl. In Biochemistry and Chemistry, the tertiary structure of a Protein or any other Macromolecule is its three-dimensional structure as defined Transmissible spongiform encephalopathies' ( TSEs, also known as prion diseases) are a group of progressive conditions that affect the Brain and Richard Lee Rhodes (b July 4, 1937) is an American journalist historian and author of both fiction and non-fiction (which he prefers to call "verity" 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. [50] The Family That Couldn't Sleep by D. T. Max provides a history of prion diseases for a popular audience.

References

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External links

Dictionary

prion

-noun

  1. The etiologic agent of transmissible spongiform encephalopathies. The only self-replicating cause of disease known to lack nucleic acids.
  2. A self-propagating alternative conformer of any protein.
  3. A petrel from the genus Pachyptila.
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