F. Explain how bovine spongiform encephalopathy (BSE) works at a molecular level by doing the following:
1. Explain the role of prions in BSE, including each of the following: * how prions are formed * the connection between misfolding and aggregation * how prions lead to the disease
A prion is a protein where the amino acid sequence or primary structure remains unchanged from that of a normal protein but the conformation has been changed by misfolding at the secondary and tertiary levels of protein structure. Bovine Spongiform Encephalopathy or BSE is a disease caused by prions. The prion which causes BSE is called PRPSC. It is the misfolded variety of the native protein PRPC.
Prions are contagious. When the abnormally folded protein comes in contact with the native protein, it will cause the normally folded proteins to change their conformation to the misfolded form.
The BSE prion’s changed shape or conformation causes it to be hydrophobic and therefore insoluble. The prion’s hydrophobic nature causes it to clump together or aggregate with the other hydrophobic BSE prions. These insoluble proteins aggregate or build up in the tissue and form a plaque. The plaques form on the cell membrane leading to cell death.
In BSE, the cells affected are the neurons of the brain and nervous system. As the prions aggregate on the cell membrane, the neurons of the brain die leaving holes in the brain tissue that give it a sponge-like appearance. This is where the disease gets the denotation “spongiform.” As neurons continue to die off, the brain deteriorates to the point of death of the organism.
2. Explain one possible role of a chaperone protein in BSE, including each of the following: * how chaperones normally act in the cell * how a chaperone protein can contribute to BSE
The function of a chaperone protein is to prevent misfolding in nascent protein. Within the cell, as the amino acid chain comes off the ribosome, a chaperone protein will bind to it to cause the conformation or folding to occur in a very specific way. For example, a particular chaperone in mammals prevents misfolding by its particular donut shape in which the chaperoned protein sits within the donut hole and is prevented from interacting with other molecules.
In BSE, it is hypothesized that the PRPSC prion acts as a chaperone in the production of more PRPSC. Theoretically the BSE prion would interfere with the normal conformation of the amino acid chain as it is being synthesized at the ribosome. This theory explains how introduction of the infectious PRPSC prion causes native proteins to change their conformation. In addition to production of the plaque causing infectious PRPSC, which will eventually destroy the cell, the cell is also deprived of the functional PRPC.
3. Recommend two ways that a country without regulations in place can decrease the risk of transmitting the prion involved in BSE (e.g., feeding practices, animal disposal).
BSE is a contagious disease which primary affects the nervous system and the nerve tissues of the body. The outbreak of BSE in the UK appears to have been caused by feeding cattle with animal protein derived from sheep with a preexisting prion disease called Scrappie.
To prevent the spread of BSE from animal to animal, the first regulation suggested is to ban the use of all animal nerve tissue including the brain and spinal column from use in animal or veterinary feed. In addition, all animals with suspected or confirmed BSE should be destroyed and their remains should be excluded from all food systems.
To prevent the spread of the disease to humans, again the recommendation is that the brain and spinal cords of all animal should be removed prior to processing meat for human consumption such as ground beef or sausage. Educational programs would inform the general population of the dangers of eating the brain which is an organ meat consumed in many countries. It would emphasize the greater safety of choosing muscle meats instead. While testing of all cattle intended for human consumption is done in some countries, this is an expensive option and will not be economically feasible in developing nations.
References
Helmenstine, A. (n.d.). What You Need to Know About Bovine Spongiform Encephalopathy. Retrieved January 3, 2016, from http://chemistry.about.com/cs/howthingswork/a/aa122703a.htm
Prevention Measures against BSE Spread. (2015, February 10). Retrieved January 3, 2016, from http://www.cdc.gov/prions/bse/prevention.html
Prions. (n.d.). Retrieved January 3, 2016, from http://www.wiley.com/legacy/college/boyer/0470003790/cutting_edge/prions/prions.htm
Thomasson, W. (n.d.). Retrieved January 3, 2016, from http://www.faseb.org/portals/2/pdfs/opa/protfold.pdf
