Bovine Spongiform Encephalophathy
Abstract: Bovine spongiform encephalopathy is caused by a prion, which is an infectious agent comprised solely of protein. The prion is a degenerate form of a normal cellular protein found in the brain and in nervous tissue. It targets the normal protein and causes the normal protein to change its shape. When enough of the prion is produced, the cell dies and symptoms of the disease are expressed.
Bovine spongiform encephalopathy (BSE), more commonly known as mad cow disease, is an unusual disease in regards to the fact that it is not caused by bacteria, viruses, fungi, or any other organism. Instead the disease is caused by prions, infectious agents simply composed of protein. Prions lack nucleic acid and are composed of an abnormal isoform of a normal cellular protein. What this means is that the prions and the cellular proteins have the same arrangements of the amino acids; however, the prion is folded differently from the cellular protein. "They are much like the toy "Transformers" that intrigued little kids in the 1980s. A sphynx could become a robot; a bug could become a warrior. Nothing was added; nothing subtracted."(Ruth Levy Guyer, Ph.D., 1) The tightly wound alpha helixes (figure 2) of the normal cellular proteins are unfolded and turn into beta sheets (figure 1).
(Ruth Levy Guyer, Ph.D., 1)
Figure 1
Figure 2
Another feature of the prion is its ability to remain stable in extreme conditions. Because prions do not have any DNA or RNA like other infectious agents, they are very hard to deal with. Prions are extremely resistant to conventional procedures to inactivate them including irradiation, boiling, dry heat, and chemicals such asformalin, betapropiolactone, and alcohols.
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...is a disease that runs in families and prevents people from sleeping, causes motor and emotional problems, and is eventually a killer. GSS was linked to two mutations in the prion gene in 1989. Prion fragments accumulate in the brain in
structures called plaques. In Alzheimer's disease, similar plaques develop, but they are composed of fragments of a different protein.
Works Cited
“Prion” Wikipedia. 28 July 2006 < http://en.wikipedia.org/wiki/Prion>.
DeArmond, Stephen J., M.D., Ph.D., Safar, Jiri, M.D., Groth, Darlene, A.B., Prusiner, Stanley B., M.D. “Prions” Office of Health and Safety. 28 July 2006 < www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4s7d.htm>.
Guyer, Ruth Levy, Ph.D. “Prions: Puzzling Infectious Proteins” National Institutes of Health Office of Science. 28 July 2006 < science.education.nih.gov/nihHTML/ose/snapshots/multimedia/ritn/prions/prions1.html>.
Creutzfeldt - Jakob disease (CJD) belongs to a family of human and animal diseases known as the transmissible spongiform encephalopathies (TSEs). Spongiform refers to the distinctive look of contaminated brains, which become filled with holes until they bear a resemblance to sponges when seen under a microscope.
PrP can occur in two forms- a normal cellular prion protein known as PrPc and a pathogenic misfolded conformer known as PrPsc. The abnormal PrPsc differs from the normal prion protein PrPc in both secondary and tertiary structure. PrPsc is principally rich in Beta sheet contents but PrPc is principally rich in alpha helical contents. Due to this difference of between the isoforms, prions are extremely resistant to certain decontamination systems. The Two tables below outline both human and animal diseases (2).
Chronic Wasting Disease (CWD) is a fatal neuro-degenerative, transmissible spongiform encephalopathy (TSE) of the family Cervidae (Hamir, et.al., 2006). The family Cervidae includes mule deer, Odocolileus hemionus, white-tailed deer, Odocolileus virginianus, Rocky Mountain elk, Cervus elaphus nelsoni, and moose, Alces alces shirasi, among others (Sigurdon & Aguzzi, 2007). CWD is a prion disease, meaning it is a protein caused infection, that occurs naturally in the deer family (Song & Lawson, 2009). This protein is suspected to be an abnormal isoform (PrPSc) of the naturally occurring host prion protein (PrPC) (Blanchong, et. Al., 2009). Bovine spongiform encephalopathy (BSE), mad cow disease, is a similar prion effecting cattle as CWD affects Cervidae. Although, scientists are not sure of transmission route it is suspected that CWD is transmissible and infectious through direct contact with infected individuals or through environmental contamination (Song & Lawson, 2009). Tests have been performed showing susceptibility of altered mice to oral transmission, mimicking the suspected route of entry, and the incubation appears slower but lasts longer with oral infection (Trifilo, et.al., 2007). The approximate time from the initial infection to death is three years.
Chronic Wasting Disease is a highly transmissible, deadly neurodegenerative disease that affects cervids in North America (Belay et al., 2004; Saunders et al., 2012). There are only four types of cervid that are known to get this disease which include elk, mule deer, white-tailed deer, and moose (Chronic Wasting Disease Alliance). It has been classified has a transmissible spongiform encephalopathy (TSE), otherwise known as a prion disease (Belay et al., 2004). A prion is an irregular, pathogenic agent that causes abnormal folding of specific proteins called prion proteins. These proteins are mostly located in the brain (Chronic Wasting Disease Alliance). The abnormal folding of this protein causes neurodegenerative diseases in a variety of species including humans, sheep, cattle, and deer (Abrams et al., 2011).
Soto, C. (2006). Prions: The New Biology of Proteins. Taylor & Francis Group: CRC Press.
Prion proteins are small infectious particles that are formed by the miss-folding of the protein structure. It is believed the miss-folding of such proteins has been the cause of disease such as Bovine spongiform encephalopathy in cows and Creutzfeldt-Jakob disease in humans. The prion proteins that are known to mankind so far suggest that they affect the brain of the affected individual. “A study1 in the British Medical Journal reveals that 1 in 2,000 people in the United Kingdom might harbour the infectious prion protein that causes variant Creutzfeldt–Jakob disease (vCJD).”(Callaway, 2013). The study therefore shows that a high number of people are at risk and this is a cause for concern as the prion protein which is miss-folded prompts normal proteins present in the brain, to alter their structure so they also become miss folded. The miss folded structure is understood to be very stable and as levels of the protein build up within the infected tissue this results in destruction and eventually death of the cell. The prion protein, PrP is thought to be the cause of all mammalian prion diseases but the structure of the protein is yet to be discovered. The normal cellular form of the prion protein is PrPc, whereas the miss folded scrapie form is PrPSc. PrPc is constructed from 209 amino acids and one disulphide bond and are found on cell membranes. “Several topological forms exist; one cell surface form anchored via glycolipid and two transmembrane forms.”(Hedge et al, 1998). The miss folded form, PrPSc has more Beta sheets however the normal form PrPc has Alpha structure present. “Fourier-transform infrared (FTIR) spectroscopy demonstrated that PrPC has a high alpha-helix content (42%) and no beta-sheet (3%), findings that were c...
Autopsies of affected cattle reveal holes in the brain tissue that give it a spongy, or spongiform, texture. Similar spongiform diseases have been recognized in humans (for example, Creutzfeldt-Jakob disease or CJD) for over a century and in sheep (scrapie) for over 200 years. The cause of BSE is unproven, although there is strong evidence that prions, which may be infective proteins, are the agent. Other hypotheses suggest that prions work with an as yet undetected virus to cause the infection.
If you had to choose between having Mad Cow Disease or becoming the top scientist in your field, which would you choose? The answer is obvious. Most realize that Mad Cow Disease, i.e. Bovine spongiform encephalopathy, is a fatal disease that has been present among cattle populations in Europe over the past couple decades. In BSE, brain cells begin to die, forming sponge-like holes in the cow’s brain tissue. Evidence shows that consumption of infected cattle could correspond with the contraction of Creutzfeldt-Jakob Disease (CJD), a similar disease in humans. Although few people have been diagnosed with CJD worldwide, they remain fearful of showing symptoms of CJD; commonly resulting in death within a year. For this reason, many Americans panicked when becoming aware that the first case of BSE was discovered in the United States in December of 2003. Unfortunately, the media is quick to show infected cows, distempered and shaking in their stalls, without giving sufficient information of the disease’s origin or the preventative measures being taken to halt its spreading. Before consumers restrict beef intake from their diets they should consider their risks. In America, chances of developing BSE is far slimmer than becoming infected with other food-borne illnesses. Although many Americans were recently startled by a reported case of Mad Cow Disease in the United States, they are assured protection from infection by: consumption of selected meats, closely guarded packaging plants, and regulation in beef imports.
clumps of abnormal proteins insides the brain cells. These proteins are called the Tau proteins they take a form of picks bodies. This slowly leads to frontotemporal dementia.
Prion Disease is an illness that many have not heard about. This is sad because many have died and are dying from this disease that doesn’t yet have a cure. “Prion Disease is a group of conditions that affect the nervous system in humans and animals… these conditions impair brain functions, causing changes in memory, personality, and behavior; a decline in intellectual function (dementia); and abnormal movements particularly difficulty with coordinating movements (ataxia)” (Genetics Home Reference). This is basically the definition of what Prion Disease is and without going into depth it explains how it affects the person that is affected. “In t...
A prion is a protein with a three-dimensional shape, as opposed to standard proteins. When a prion comes into contact with another protein, that protein transforms into another prion. Eventually, as more proteins come into contact with prions, the host will show symptoms of a severe and ultimately fatal illness. Common diseases caused by prions would be Bovine Spongiform Encephalopathy (known informally as “Mad Cow disease”), and Crutzfeldt-Jakob disease. There are also strains of diseases infecting other mammals as well, including Elk (Chronic Wasting disease) and Mink (Transmissible Mink Encephalopathy). One common connection is that all prion-caused diseases primarily damage the brain tissue of the patient. All known prion diseases are fatal, and have no cure or treatment.
Creutzfeldt-Jakob Disease is an uncommon, deteriorating, consistently fatal brain disorder that is caused by prions. The symptoms of CJD are similar of Alzheimer’s but progress much faster. There are three variations of CJD, sporadic, familial, and acquired. All variations affect the brain the same way and have the same result of death. CJD is an untreatable and incurable disease.
Nuclear magnetic resonance (NMR) of concentrated PrPC solutions was used to determine its exact shape. Analysis revealed a secondary structure that includes one 4 amino-acid (AA) and one 3AA 훽-sheet, and one each of 11AA, 22AA and 28AA α-helices.1 Studying the PrPSc form has proven difficult because of its formation of disordered aggregates. The knowledge that we do have about this pathogenic form is derived from electron crystallography, and computer modeling, and reveals, while still having the same number of 훽-sheets and α-helices, a more heavily 훽-pleated sheet dominated structure.1 This change in conformation causes the PrPSc to be insoluble in non-ionic detergents, as well as resistant to degradation by proteinase K. PrPSc can either be formed by spontaneous conversion of PrPC to PrPSc, or by exposure of PrPC to PrPSc. The conformational conversion of the prion protein has been hypothesized as being related to the unstructured N-terminal domain, and specifically, a 21 nucleotide region termed the “toxic-peptide”, of PrPSc.1 This small region received its name because its introduction to other proteins induces 훽-sheet structured fibrils formation, and is known to damage the mouse hippocampus. Narrowing down the mutagenic segment of this peptide has lead researches to a small portion within the N-terminal domain, specifically in the hydrophobic-core, with the
On a closing note, prion research is significant not only for possible breakthroughs in understanding TSEs, but because of the vast implications the very concept of prions holds for the entire field of biology. As the first substance discovered that can replicate in the absence of nucleic acids, prions defy one of the most central biological doctrines. The similarities between TSEs and dementia disorders like Alzheimer’s disease and “findings of proteins with a prion-like behavior in yeast and other fungi” (Soto, 2006, 143) suggest that prions and proteins like them may be much more common than ever expected (Soto, 2006, 154).
This article was written by Jason Hayes on July 26, 2012 about a disease that you can get from eating human brains or just human flesh, but it is mostly found in the brain. The premis of this article was the foundation of most molecular biology