Transmissible spongiform encephalopathy Classification and external resources
ICD-10	A81.
ICD-9	046
DiseasesDB	25165
eMedicine	neuro/662
MeSH	D017096

Transmissible spongiform encephalopathies (TSEs, also known as prion diseases) are a group of progressive conditions that affect the brain and nervous system of animals. 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 A00-A79 - Bacterial infections and other intestinal infectious diseases and STDs (A00-A09 Intestinal Infectious diseases ( 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. The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain The nervous system is a Network of specialized cells that communicate information about an animal's surroundings and itself According to the most widespread hypothesis they are transmitted by prions, though some other data suggest an involvement of a Spiroplasma infection^[1]. A prion (ˈpriːɒn is thought to be an infectious agent that according to current scientific consensus is comprised entirely of a propagated, mis-folded Spiroplasma is a genus of Mollicutes, a group of small Bacteria without Cell walls Spiroplasma shares the simple Metabolism Mental and physical abilities deteriorate and myriad tiny holes appear in the cortex causing it to appear like a sponge (hence 'spongiform') when brain tissue obtained at autopsy is examined under a microscope. The cerebral cortex is a structure within the Brain that plays a key role in Memory, Attention, perceptual Awareness, Thought, An autopsy, also known as a post-mortem examination, necropsy, or obduction, is a Medical procedure that consists of a thorough Examination A microscope ( Greek: ( micron) = small + ( skopein) = to look or see is an instrument for viewing objects that are The disorders cause impairment of brain function, including memory changes, personality changes and problems with movement that worsen over time. Prion diseases of humans include classic Creutzfeldt-Jakob disease, new variant Creutzfeldt-Jakob disease (a human disorder related to mad cow disease), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia and kuru. Creutzfeldt-Jakob disease ( CJD) is a very rare and incurable degenerative neurological disorder ( Brain Disease) that is ultimately Bovine Spongiform Encephalopathy ( BSE) commonly known as Mad-Cow Disease ( MCD) is a fatal Neurodegenerative disease in Cattle 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 These conditions form a spectrum of diseases with overlapping signs and symptoms.

Unlike other kinds of infectious disease which are spread by microbes, the infectious agent in TSEs is a specific protein called prion protein. A microorganism (also spelled micro organism or micro-organism and also called a microbe) is an Organism that is Microscopic (usually Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl A prion (ˈpriːɒn is thought to be an infectious agent that according to current scientific consensus is comprised entirely of a propagated, mis-folded Misshaped prion proteins carry the disease between individuals and cause deterioration of the brain. The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain TSEs are unique diseases in that their aetiology may be genetic, sporadic or infectious via ingestion of infected foodstuffs and via iatrogenic means (e. Etiology (alternatively aetiology, aitiology) is the study of causation. The terms iatrogenesis and iatrogenic artifact refer to adverse effects or complications caused by or resulting from medical treatment or advice g. blood transfusion). ^[2] Most TSEs are sporadic and occur in an animal with no prion protein mutation. Inherited TSE occurs in animals carrying a rare mutant prion allele, which expresses prion proteins that contort by themselves into the disease-causing conformation. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism An allele (ˈæliːl (UK /əˈliːl/ (US (from the Greek αλληλος allelos, meaning each other) is one member of a pair or series of different forms Proteins are an important class of biological Macromolecules present in all biological organisms made up of such elements as Carbon, Hydrogen Transmission occurs when healthy animals consume tainted tissues from others with the disease. In recent times a type of TSE called bovine spongiform encephalopathy (BSE) spread in cattle in an epidemic fashion. 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 This occurred because cattle were fed the processed remains of other cattle, a practice now banned in many countries. The epidemic could have begun with just one cow with sporadic disease.

Prions cannot be transmitted through the air or through touching or most other forms of casual contact. However, they may be transmitted through contact with infected tissue, body fluids, or contaminated medical instruments. Normal sterilization procedures such as boiling or irradiating materials fail to render prions non-infective. Sterilization (or sterilisation, see spelling differences) refers to any process that effectively kills or eliminates transmissible agents (such as Fungi

Contents 1 Classification 2 Features of TSE 3 Genetics 4 Competing Hypotheses 4.1 Viral Hypothesis 4.2 Protein-Only Hypothesis 5 Epidemiology 6 Possible cure or vaccine 7 Notes 8 References 9 External links

Classification

Mammalian agents of spongiform encephalopathies

ICTVdb Code	Disease name	Natural host	Prion name	PrP isoform
90.001.0.01.001.	Scrapie	Sheep and goats	Scrapie prion	OvPrPSc
90. Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands A protein isoform is a version of a Protein with only small differences to another isoform of the same protein 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 001. 0. 01. 002.	Transmissible mink encephalopathy (TME)	Mink	TME prion	MkPrPSc
90. 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. 001. 0. 01. 003.	Chronic wasting disease (CWD)	Elk, White-tailed deer, Mule Deer and Red Deer	CWD prion	MDePrPSc
90. 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 White-tailed deer ( Odocoileus virginianus) also known as the Virginia deer, or simply as the whitetail, is a medium-sized Deer found throughout The mule deer ( Odocoileus hemionus) is a Deer whose habitat is in the western half of North America. The Red Deer ( Cervus elaphus) is one of the largest Deer species 001. 0. 01. 004.	Bovine spongiform encephalopathy (BSE)	Cattle	BSE prion	BovPrPSc
90. 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 001. 0. 01. 005.	Feline spongiform encephalopathy (FSE)	Cats	FSE prion	FePrPSc
90. 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 001. 0. 01. 006.	Exotic ungulate encephalopathy (EUE)	Nyala and greater kudu	EUE prion	NyaPrPSc
90. The Nyala ( Tragelaphus angasii) is a South African Antelope. The Greater Kudu ( Tragelaphus strepsiceros) is a Woodland Antelope found throughout eastern and southern Africa. 001. 0. 01. 007.	Kuru	Humans	Kuru prion	HuPrPSc
90. Kuru is a disease which affects the Brain. It was endemic among the Fore tribe of Papua New Guinea and was universally fatal Human beings, humans or man (Origin 1590–1600 L homō man OL hemō the earthly one (see Humus 001. 0. 01. 008.	Creutzfeldt-Jakob disease (CJD)	Humans	CJD prion	HuPrPSc
	(New) Variant Creutzfeldt-Jakob disease (vCJD, nvCJD)	Humans	vCJD prion	HuPrPSc
90. Creutzfeldt-Jakob disease ( CJD) is a very rare and incurable degenerative neurological disorder ( Brain Disease) that is ultimately 001. 0. 01. 009.	Gerstmann-Sträussler-Scheinker syndrome (GSS)	Humans	GSS prion	HuPrPSc
90. Gerstmann-Sträussler-Scheinker syndrome (GSS is a very rare usually familial fatal neurodegenerative Disease that affects patients from 20 to 60 years in age 001. 0. 01. 010.	Fatal familial insomnia (FFI)	Humans	FFI prion	HuPrPSc

Features of TSE

The degenerative tissue damage caused by human prion diseases (CJD, GSS, and kuru) is characterised by four features: spongiform change, neuronal loss, astrocytosis and amyloid plaque formation. Fatal familial insomnia (FFI is a very rare autosomal dominant inherited Prion Disease of the Brain. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Astrocytes (also known collectively as astroglia) are characteristic star-shaped glial cells in the Brain and Spinal cord. Amyloids are insoluble fibrous Protein aggregates sharing specific structural traits These features are shared with prion diseases in animals, and the recognition of these similarities prompted the first attempts to transmit a human prion disease (kuru) to a primate in 1966, followed by CJD in 1968 and GSS in 1981. A primate is a member of the biological order Primates ( Latin: "prime first rank" the group that contains Lemurs the Aye-aye These neuropathological features have formed the basis of the histological diagnosis of human prion diseases for many years, although it was recognized that these changes are enormously variable both from case to case and within the central nervous system in individual cases. Histology (from the Greek = 'tissue' is the study of the microscopic anatomy of cells and tissues of Plants and In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. ^[3]

The clinical signs in humans vary, but commonly include personality changes, psychiatric problems such as depression, lack of coordination, and/or an unsteady gait (ataxia). Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression Ataxia (from Greek α- as a negative prefix + -τάξις, meaning "lack of order" is a neurological sign and symptom consisting Patients also may experience involuntary jerking movements called myoclonus, unusual sensations, insomnia, confusion, or memory problems. Myoclonus (maɪˈɒklənəs is brief involuntary twitching of a Muscle or a group of muscles Insomnia is a symptom of a sleeping disorder characterized by persistent difficulty falling asleep or staying asleep despite the opportunity In the later stages of the disease, patients have severe mental impairment (dementia) and lose the ability to move or speak. Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline ^[4]

Early neuropathological reports on human prion diseases suffered from a confusion of nomenclature, in which the significance of the diagnostic feature of spongiform change was occasionally overlooked. The subsequent demonstration that human prion diseases were transmissible reinforced the importance of spongiform change as a diagnostic feature, reflected in the use of the term "spongiform encephalopathy" for this group of disorders.

Prions appear to be most infectious when in direct contact with affected tissues. For example, Creutzfeldt-Jakob disease has been transmitted to patients taking injections of growth hormone harvested from human pituitary glands, and from instruments used for brain surgery (Brown, 2000) (prions can survive the "autoclave" sterilization process used for most surgical instruments). Growth hormone ( GH) is a Peptide hormone that stimulates growth and cell reproduction in humans and other animals The pituitary gland, or hypophysis, is an Endocrine gland about the size of a Pea. Neurosurgery is the surgical discipline focused on treating those central, Peripheral nervous system and spinal column diseases amenable to surgical An autoclave is a pressurized device designed to heat aqueous solutions above their Boiling point at normal atmospheric pressure to achieve sterilization It is also believed that dietary consumption of affected animals can cause prions to accumulate slowly, especially when cannibalism or similar practices allow the proteins to accumulate over more than one generation. Cannibalism (from Spanish es ''caníbal'' in connection with cannibalism among the Antillean Caribs, also called anthropophagy (from Greek ἄνθρωπος An example is kuru, which reached epidemic proportions in the mid 20th century in the Fore people of Papua New Guinea, who used to consume their dead as a funerary ritual. Kuru is a disease which affects the Brain. It was endemic among the Fore tribe of Papua New Guinea and was universally fatal The Fore live in the Okapa District of the Eastern Highlands Province, Papua New Guinea. Papua New Guinea (or ˈpæpjuːə in Tok Pisin: Papua Niugini) officially the Independent State of Papua New Guinea, is a country in Oceania ^[5] Laws in developed countries now proscribe the use of rendered ruminant proteins in ruminant feed as a precaution against the spread of prion infection in cattle and other ruminants. Rendering is a process that converts waste animal tissue into stable value-added materials Physiologically a ruminant is a Mammal of the order Artiodactyla that digests plant-based food by initially softening it within the animal's first stomach known

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). Encephalopathy /ɛnˌsɛfəˈlɒpəθi/ literally means Disease of the Brain. Progressive multifocal leukoencephalopathy (PML also known as progressive multifocal leukoencephalitis is a rare and usually fatal viral disease that is characterized by progressive The JC virus or John Cunningham virus (JCV is a type of human Polyomavirus (formerly known as papovavirus and is genetically similar to BK virus and SV40 CADASIL ( c erebral a utosomal d ominant a rteriopathy with s ubcortical i nfarcts and l eukoencephalopathy is the Krabbe disease (also known as globoid cell leukodystrophy or galactosylceramide lipidosis) is a rare often fatal degenerative disorder that affects the Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins PSL -- which is a spongiform encephalopathy -- is also probably not caused by a prion, although the adulterant which causes it among heroin smokers has not yet been identified. Heroin ( INN: diacetylmorphine, BAN: diamorphine) is a semi-synthetic opioid synthesized from Morphine, a derivative ^[6][7][8][9] This, combined with the highly variable nature of prion disease pathology, is why a prion disease cannot be diagnosed based solely on a patient's symptoms.

Genetics

Mutations in the PRNP gene cause prion disease. PRNP ( PRioN Protein (Creutzfeld-Jakob disease Gerstmann-Sträussler-Scheinker syndrome fatal familial insomnia) is a Gene that provides instructions to make a History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance Familial forms of prion disease are caused by inherited mutations in the PRNP gene. Only a small percentage of all cases of prion disease run in families, however. Most cases of prion disease are sporadic, which means they occur in people without any known risk factors or gene mutations. Rarely, prion diseases also can be transmitted by exposure to prion-contaminated tissues or other biological materials obtained from individuals with prion disease.

The PRNP gene provides the instructions to make a protein called the prion protein (PrP). PRNP ( PRioN Protein (Creutzfeld-Jakob disease Gerstmann-Sträussler-Scheinker syndrome fatal familial insomnia) is a Gene that provides instructions to make a Normally, this protein may be involved in transporting copper into cells. It may also be involved in protecting brain cells and helping them communicate. 24 Point-Mutations in this gene cause cells to produce an abnormal form of the prion protein, known as PrP^Sc. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism This abnormal protein builds up in the brain and destroys nerve cells, resulting in the signs and symptoms of prion disease.

Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent.

In some people, familial forms of prion disease are caused by a new mutation in the PRNP gene. Although such people most likely do not have an affected parent, they can pass the genetic change to their children.

Competing Hypotheses

Viral Hypothesis

This hypothesis postulates that an infectious viral agent is the cause of the disease. Evidence for this hypothesis is as follows:

• Incubation time is comparable to a lentivirus
• Strain variation of different isolates of PrPsc^[10]
• An increasing titre of PrPsc as the disease progresses suggests a replicating agent.

This hypothesis is largely discredited, as no infectious, non-human nucleic acid has ever been isolated from the disease. It is largely based on the fact that infectious agents have previously been viral in origin, preferring this as more plausible than the infectious protein hypothesis.

Protein-Only Hypothesis

Protein could be the infectious agent, inducing its own replication by causing conformational change of normal cellular PrPC into PrPsc. Evidence for this theory:

• infectivity titre correlates with PrPSc levels. However, this is disputed. ^[11]
• PrPSc is an isomer of PrPC
• Denaturing PrP removes infectivity ^[12]
• Recombinant PrP is infectious ^[13]
• PrP-null mice cannot be infected^[14]

Epidemiology

These spontaneous disorders in humans are very rare affecting only about one person per million worldwide each year. However, transmissible TSEs can reach epidemic proportions as was seen in the UK BSE outbreak of the 80s and 90s. It is very hard to map the spread of the disease due to the difficulty of identifying individual strains of the prions. This means that if animals start to show the disease after an outbreak on a nearby farm then you cannot show that it is the same strain affecting both, suggesting transmission, or that the second outbreak came from a completely different source.

Possible cure or vaccine

Recent research from the University of Toronto and Caprion Pharmaceuticals have discovered one possible avenue which might lead to quicker diagnosis, a vaccine or possibly even treatment for prion diseases. This article is about the University of Toronto's St George Campus The abnormally folded proteins which cause the disease have been found to expose a side chain of amino acids which the properly folded protein does not expose. A side chain in Organic chemistry and Biochemistry is a part of a Molecule that is attached to a core structure Antibodies specifically coded to this side chain amino acid sequence have been found to stimulate an immune response to the abnormal prions and leave the normal proteins intact. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily ^[15]

Another idea involves using custom peptide sequences. Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino Since some research suggests prions aggregate by forming beta barrel structures, work done in vitro has shown that peptides made up of beta barrel-incompatible amino acids can help break up accumulations of prion. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this Yet a third idea concerns genetic therapy, whereby the gene for encoding protease-resistant protein is considered to be an error in several species, and therefore something to be inhibited. Gene therapy is the insertion of Genes into an individual's cells and tissues to treat a Disease, and Hereditary diseases in which a History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance

Notes

References

• This entry incorporates public domain text originally from the National Institute of Neurological Disorders and Stroke, National Institutes of Health [1] and the U.S. National Library of Medicine [2]

• Montagna P, Gambetti P, Cortelli P, Lugaresi E (2003). "NIH" redirects here For other meanings of NIH see NIH (disambiguation. The United States National Library of Medicine ( NLM) operated by the United States federal government, is the world's largest Medical library. "Familial and sporadic fatal insomnia". Lancet Neurol 2 (3): 167-76. PMID 12849238.  
• Prusiner SB (2001). "Shattuck lecture--neurodegenerative diseases and prions". N Engl J Med 344 (20): 1516-26. PMID 11357156.  
• Weissmann C (2004). "The state of the prion". Nat Rev Microbiol 2 (11): 861-71. doi:10.1038/nrmicro1025. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15494743.  

External links

• Transmissible Spongiform Encephalopathy
• Neurodegenerative Disease.
• Neurodegenerative disease: Encephalopathy.
• UK CJD Surveillance Unit Statistics for prion disease in the UK, information on TSEs, and a comprehensive list of other links.
• Creutzfeldt-Jakob Disease Foundation Offers support and information concerning Creutzfeldt-Jakob Disease.
• Mad Cow Disease Info from the Center for Global Food Issues
• The Pathological Protein - Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases (2003, updated online 2005). Philip Yam, Scientific American magazine writer and News Editor. Scientific American is a Popular science magazine, published (first weekly and later monthly since August 28, 1845, making it
• European Symposium
• American Symposium

© 2009 citizendia.org; parts available under the terms of GNU Free Documentation License, from http://en.wikipedia.org
Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic