Transmissible spongiform encephalopothies, (TSEs) or prion diseases, are a group of neurodegenerative diseases present in humans and animals which have been discussed in recent years due to a new variant of the a human TSE variant Creutzfeldt Jakob Disease (vCJD) which have corresponded with cases of bovine spongiform encephalopathy. TSEs are always fatal and rapidly degenerative after a long incubation period. They are characterized by the effect they have on brain tissue: sponge-like degeneration of tissue, astrogliosis and neuron loss all in the absence of an inflammatory reaction. In humans this manifests itself typically through memory loss, motor problems such as trembling, dementia and personality changes. Prions have fascinated researchers for decades after their discovery, until Prusiner identified and defined prion diseases in 1982 (Prusiner, 1995). Prusiner (1991) classified a prion as an infectious particle composed of a protein that causes neurodegenerative disorders that are all fatal. These diseases are often called, spongiform encephalopathies because they typically cause the brain to become spongy and filled with holes (Prusiner, 1995).
Because the infectious agent in TSEs is a, protein, they are transmissible through ingestion of infected tissue and blood transfusion. The infected protein or prion can also be genetically inherited or just show up sporadically in an individual. There are no reliable cures for prion diseases and are invariably fatal.
Experiments to identify the cause of TSEs have determined that it is a protein. They found this by determining that the infectious agent is not a virus and that it is resistant to radiation and nucleases. But, the infectivity is affected by procedures that damage proteins. There are currently competing theories to explain this class of infectious diseases, the most prominent of which is the prion theory. It is, however, unclear whether abnormal prions are the infectious agent or whether they are another symptom of the disease caused by a different, agent. It has been hypothesized that there is genetic component as well as an infectious prion agent, that a certain mutated genotype is necessary for an individual to be susceptible to infection. Viral, fungal and heavy metal toxicity hypotheses have also been proposed, but have not gained as much support as the prion theory.
The word prion is a combination of the words protein and infectious. Prions are misfolded proteins. They are theorized to be destructive because the exogenous prion protein is misfolded, or abnormally shaped and is capable of causing endogenous proteins in its host to become abnormally folded as well, which causes tissue damage. Neural damage occurs because the proteins form amyloid plaques, which, in spongiform encephalopathies leaves holes in the infected nervous tissue, which makes the tissue sponge-like. Amyloids are also responsible for damage in Parkinsons Disease, Huntingtons Disease and Alzheimers.
The misfolded state of prions is extremely stable, which is why prions are so indestructible, and why the infectious agent can be transmitted even through well-cooked meat and bone meal. In fact, the prion theory was initially formed on the basis of the resistance of Creutzfeldt Jakob to ultraviolet radiation.
After prions were discovered as an infectious agent, it was revealed that the protein that prions are made of, PrP (which stands for Prion Protein) might be necessary for normal life. The infectious prion agent, PrPSc, is an isoform of a non-infectious, normal protein; PrPc. Non-infectious normal PrP may be a necessary component of life and long-term memory preservations. Hippocampal long-term potentiation has been abnormal in animals born without the genes necessary for (non-infectious) PrP creation.
A genetic engineering company called Hematech announced in 2007 that they had developed a cow that lacks the gene necessary to create PrP and thus could not be infected by PrPSc. Hematech states that the intent of this genetic mutation was not to create a prion-protected commercial cattle, but a cow whose blood can be safely used to create blood products such as intravenous immunoglobins. The prion-free cow was funded (purchased for forty five million dollars) by Kirin, a Japanese brewing company that recently decided to diversify and expand their business to include medical products.