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Transmissible spongiform encephalopathy

From Academic Kids

Transmissible spongiform encephalopathies (TSEs) are fatal, incurable degenerative diseases of the brain transmitted by prions. 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.

Unlike other kinds of infectious disease which are spread by microbes, the infectious agent in TSEs is a specific protein called prion protein. Misshaped prion proteins carry the disease between individuals and cause deterioration of the brain. TSEs are unique diseases in that they can be inherited, occur spontaneously ("sporadic" TSE) or can be spread through infection (Collinge, 2001). Most TSEs are sporadic and occur in an animal with no prion protein mutation. Inherited TSE occurs in animals carring a rare mutant prion allele, which expresses prion proteins that contort by themselves into the disease-causing conformation. 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. This occurred because cattle were fed the processed remains of other cattle (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 the pathogens non-infective.

Contents

Known TSEs

Various zoo animals and pets have contracted TSEs, presumably through feed contaminated with tissues from infected cattle. In the laboratory, TSEs are transmissible to mice, goats and a wide range of other animals. (Collinge, 2001)

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. 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.These neuropathological features have formed the basis of the histological diagnosis of human prion diseases for many years, although it was recognised that these changes are enormously variable both from case to case and within the central nervous system in individual cases (Jeffery, 1995).

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). Patients also may experience involuntary jerking movements called myoclonus, unusual sensations, insomnia, confusion, or memory problems. In the later stages of the disease, patients have severe mental impairment (dementia) and lose the ability to move or speak (Collinge, 2001).

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). 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. 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 (Collins, 2001). 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.

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). 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 ([1] (http://www.hafci.org/infoline/enu/heroin.htm), [2] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10563626&dopt=Abstract), [3] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9308333&dopt=Abstract), [4] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11965173&dopt=Abstract)). 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.

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 treatement for prion diseases. The abnormally folded prions which cause the disease have been found to expose a side chain of amino acids which the properly folded prion does not expose. 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 prions intact. [5] (http://www.sciencedaily.com/releases/2003/06/030602025719.htm)

Another idea involves using custom peptide sequences. Since some research suggests abnormal 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.

References

  • This entry incorporates public domain text originally from the National Institute of Neurological Disorders and Stroke, National Institutes of Health. [6] (http://www.ninds.nih.gov/health_and_medical/disorders/tse.htm)
  • Brown P, et al (2000). Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 55 (8), 1075-1081 [7] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11071481&query_hl=6)
  • Collinge J (2001). Prion diseases of humans and animals: their causes and molecular basis. Ann. Rev. Neurosci. 24, 519-550 [8] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11283320&query_hl=8)
  • Collins S, et al (2001). Gerstmann-Sträussler-Scheinker syndrome, Fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies. J. Clin. Neurosci. 8 (5), 387-397 [9] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11535002&query_hl=10)
  • Jeffery M, Goodbrand IA, Goodsir CM (1995). Pathology of the transmissible spongiform encephalopathies with special emphasis on ultrastructure. Micron 26 (3), 277-298 [10] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7788281&query_hl=19)

External link

Mad Cow Disease (http://www.mad-cow-facts.com) Info from the Center for Global Food Issuesda:TSE de:Prionerkrankung pl:Zakaźne encefalopatie gąbczaste

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