Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that are thought to be caused by the misfolding of prion proteins. Prions are able to replicate in the absence of nucleic acids. TSEs include: scrapie, bovine spongiform encephalopathy, Creutzfeldt-Jakob disease, kuru, Gerstmann-Straussler-Scheinker disease, and Fatal Familial Insomnia. They can affect many different animals, including humans. Currently, there are no ways to diagnose, treat, or cure TSEs, as much more research is needed before these diseases are completely understood.
Prions are a type of protein found naturally in the brain and other regions of the central nervous system. The diseases associated with prions are collectively known as transmissible spongiform encephalopathies (TSEs). “Transmissible” refers to their potentially infectious nature, and “spongiform encephalopathies” indicates the microscopic sponge-like deterioration of the brain caused by the progression of the disorders. While these fatal neurodegenerative diseases exhibit different clinical symptoms, have different incubation periods, and even target different areas of the brain, they do share a number of characteristics. They occur in both animals and humans. During a silent incubation period, there are no detectable signs of the disease, although depending on the specific disease, the length of the incubation period can “vary from a few weeks to up to 40 [years]” (Baker & Ridley, 1996, 1). Due to their unique method of propagation (which will be addressed later), TSEs present a seeming paradox in that “inherited cases give rise to a disease that is transmissible but acquired cases do not produce heritable diseases” (Baker & Ridley, 1996, 1). Most important, these disorders are grouped together because they share one significant molecular element: the misfolded prion protein.
2. The Prion Protein and Its Function
The prion protein (PrP) is unusual in that it has two stable isoforms. The cellular or normal form of the prion protein is termed PrPC, while the disease form is termed PrPSC. Sharing the same sequence of amino acids, or primary structure, PrPC and PrPSC differ in their secondary, tertiary, and quaternary structures. The normal prion protein has N- and C-terminals, three alpha helices, and two beta sheets (Soto, 2006, 40). Its function is still not completely understood. However, scientists have found evidence that point to various possibilities. 1) Because most PrPC are located in lipid rafts, membrane structures involved in signaling, it is suggested that PrPC may also be a mediator in neuroprotective signaling pathways. 2) Interaction between PrPC and Bcl-2, a ligand involved in protecting neurons from apoptosis, suggests the possibility that PrPC may be an antiapoptotic protein. 3) PrPC has also been linked to copper metabolism in the brain. In one particular study, PrP knockout mice, or mice that were genetically altered to...