Prions and Bse

Bovine Spongiform Encephalopathy (BSE), primarily known as Mad Cow Disease, was first detected in Great Britain in 1986. (1) Since it was first detected, there had been 181376 confirmed cases in the United Kingdom from a span of November 1986 to November 2002. (2) BSE is an extremely rare, series of fatal chronic neurodegenerative disease caused by an abnormal confirmation of the prion protein affecting the central neurons system of cattle. (1,3) Bovine Spongiform Encephalopathy is known as the general form of another disease that was found in other animals such as sheep. This disease discovered in the sheep before BSE was known as Scrapie. (4) The name of this disease was created from its literally meaning: scraping. The sheep that came in contact with this disease would exhibit behaviours of scraping themselves against trees because of the itchiness the disease caused, thus earning the name, "Scrapie." (4)

The appearance of the Scrapie disease was a new recognized form of a neurological disease. This disease is known as the TSE, Transmissible Spongiform Encephalopathy. (4) This general form of the Scrapie disease is found in cattle is one of the main causes of BSE. The spread of Scrapie is from cattle fed food with bovine tissues, such as brain and spinal cord. (2) The main cause if from the carcasses (dead body parts) of sheep that contains the agent that is contaminated with this disease. It is then transferred into humans when they also ingest contaminated food items that once belong to cattle. Other ways may also cause BSE which includes corneal transplant, other tissues, and blood transfusions from infected donors as well as contaminated equipment to perform surgery. (5)

When the cows ate remains of other animals, they passed on the Scrapie disease. When humans ate beef products, they also consume the contaminated Scrapie agent. But in humans, we call this disease, "Mad Cow Disease," because it is known that we get it from cows. But what really causes this disease to be harmful? The answer lies within a single protein called a prion protein. (4) The term "prions" refers to abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins that are found most abundantly in the brain. (6) The prion protein is a type of protein which is also known as the cellular prion protein (PrPC). (4) All mammals have this prion protein, in which the sequences are similar, but not identical. (4) This self-replicating protein can change its shape. It unknown of what this protein is used for, but many scientists believe that it is incorporated in the formation of memories. (4) Prions are transmissible particles that are devoid (entirely lacking or free from) of nucleic acid and seem to be composed exclusively of a modified protein. (PrPC) (7) In TSE, the normal PrPC is converted to an abnormal form, PrPSC. There is a theory in which in the membrane, PrPSC flips the normal PrPC to make it abnormal, along with changing its shape and confirmation. (4) This is how the prion protein is able to consistently replicate by itself while infecting other cells.

The normal prion protein, PrPC, is converted to PrPSC though a post translated process during which it requires a high -sheet content. (7) All the prion diseases, such as Scrapie and BSE, involve the changing of this prion protein. As the normal form, PrPC, changes to the abnormal form, PrPSC, it involves a confirmation change whereby the -helical content diminishes and the amount of sheet increases. (7) This transition must be accompanied by profound changes in the properties of the protein, PrPC. Some of those changes include the solubility and the digestive attributes. PrPC is soluble in non-denaturing detergents whereas PrPSC is not. Moreover, PrPC is readily digested by proteases, whereas PrPSC is partially resistant. (7) When the prion protein has changed, it causes the TSE that are found in sheep as Scrapie. As in passes on to a human being, most human afflicted with prion disease present a rapidly progressive dementia (A chronic or persistent disorder of the mental processes caused by brain disease), but some manifest a cerebellar ataxia. (A pathological inability to make coordinated movements associated with lesions to the cerebellum.) (7) Although the infected brains may appear grossly normal upon post mortem examination, it shows spongiform degeneration and astrocytic gliosis (proliferation of astrocytes in damaged areas of the central nervous system) under the microscope.

PrPSC is the only component of the infectious prion particle, but it is major. (7) The formation of PrPSC is a post translational process involving only a conformational change in PrPC. Molecular modeling studies shown that PrPC is a four-helix bundle protein containing four regions of secondary structure, denoted H1 through H4. (7) Fourier transform infrared (FTIR) and circular dichroism (CD) studies showed that PrPC contains about 40% helix and little sheet. (7) Subsequent nuclear magnetic resonance (NMR) studies of a synthetic PrP peptide containing residues 90 to 145 provided good evidence for H1. This peptide contains residues 113 to 128, the most highly conserved residues among all species studied. (7) When the peptide is extended to include helix A this forms the central domain of PrPC (approximately residues 95 to 170) that binds to PrPSC during the formation of nascent PrPSC. (7) This study shows the connection between cattle and humans versus the connection between sheep and human. This raises the possibility that prion transmission from cattle to human occurs more readily than sheep to human, which shows why ingesting beef would infect humans, and not lamb meat. (7)

There are many diseases in the human and animal that is caused by the prion disease. The common ones that occur in animals are Bovine Spongiform Encephalopathy (BSE), Chronic Wasting Disease, Scrapie, Transmissible Mink Encephalopathy, and Feline Spongiform Encephalopathy. (6) Some human forms include Creutzfeldt-Jakob Disease (CJD), Variant Creutzfeldt-Jakob Disease (vCJD), Gerstmann-Straussler-Scheinker Syndrome, Fatal Familial Insomnia and Kuru. (6) The two most important types are CJD and vCJD. The first case of CJD was reported in 1996. (5) CJD causes the brain damage that leads to a rapid disease of mental function and movement. Although this disease is rare, those who are infected experience a tremendous effect. There are 1 in a million people who get this type of disease. (5) It is usually received by people who are aged 20 to 70 with symptoms being explicit when they are around 50. (5) There are two types of this disease: classic and variant. The sporadic classic disease make up most of the CJD cases and it occurs for no reason, usually at the age of around 65. (5) The familial classic