Prion proteins are present in low levels in many tissues throughout the body and probably travel through tissues to get to the central nervous system, where they ultimately accumulate and do the most damage. The characteristic symptom of TSEs is the spongy appearance of the brain. This appearance is due to enlarged vacuoles in neurons, neuron death from protein buildup in lysosomes which burst, killing neurons, or protein build up that leads to plaque formation and neuron death. The exact way that prions lead to neurodegeneration is not known, but there are some specific characteristics of PrPSc's that give insight into the way that they cause disease. PrPSc's tend to form oligomers , which are groups of protein linked together. The linkage of proteins causes a protein build-up in the brain, creating fibrous plaques similar to those in other neurodegenerative diseases, such as Alzheimer's (Cobb, 2009). The areas of the brain in which the plaques occur depend on the different strains of TSE. Some proteins show more of an amyloid plaque. In addition, because PrPSc is much harder to break down and is often resistant to the enzymes that break down protein, it is not eliminated in the cells, as it should be, leading to even more of a build-up. Furthermore, there exists no immune response to PrPSc because it is not recognized as a foreign agent. This lack of immune response means that the body does not do anything to fight it.
Normal and Misfolded prion proteins
photo courtesy of www.cmpharmucsf.edu/cohen/research