Prion Diseases as Transmissible Zoonotic Diseases

Lee, Jeongmin; Kim, Su Yeon; Hwang, Kyu Jam; Ju, Young Ran; Woo, Hee-Jong

When PrP C comes in contact with PrP Sc , PrP C changes into a thermodynamically stable PrP Sc via protein folding; then, PrP Sc converts PrP C into another PrP Sc . After this process is repeated over time, PrP Sc accumulates in the body and results in induction of TSE [15] . Although it is not certain whether TSEs are caused by PrP Sc alone or by a complex reaction with PrP Sc and other factors, such as other proteins, nucleic acids, or pathogens [16] , it is certain that the main causative agent is PrP Sc . However, to explain the replication of PrP Sc within the body, two thermodynamically stable PrP Sc molecules must be separated and combined with other PrP C s. The animal's genetic type and other additional factors should be considered in the process [17] . Therefore, scientists assume that the hypothetical macromoleculeddesignated protein Xdmay play a role in the conversion from PrP C to PrP Sc and continue to search for candidates. At present, dozens of proteins in the cytosol, plasma membrane, extracellular matrix, and lipid rafts are known to interact with PrP C and/or PrP Sc ; however, strong evidence for the identity of protein X has not been revealed yet [18] . Identifying the existence and role of protein X, prion diseases can be prevented and/or treated. Normal PrP C , which is encoded on the gene locus PRNP in the genome of hosts, is a glycoprotein found in neuron cell membranes in animals and humans. PrP C has a w40% a-helical and w3% b-sheet conformation, whereas PrP Sc has a w30% a-helical and w40% b-sheet conformation. The conformational transition from the helices and hydrophobic regions of PrP C is a major cause of the increase of b-sheet composition in PrP Sc (Figure 1 ) [19, 20] . Since the conformational alteration from PrP C to PrP Sc is not immunogenic, the immune system of the organism can hardly distinguish the normal protein structure from the infectious prion structure, except with respect to its stability [21] . Unlike bacteria or viruses, pathogenic PrP Sc cannot be removed by regular alcohol or formalin sterilization processes, and cannot be decomposed by proteolytic enzymes. Moreover, it is resistant to heat, ultraviolet rays, and chemicals. Under three times the atmospheric pressure the materials for prion should be sterilized for more than for over an hour with 2% sodium hypochlorite and 2N sodium hydroxide at 20 C, and equipment should be sterilized for more than 12 hours with the same solution. In laboratories, materials should be disinfected for more than 4.5 hours at 132 C or for 1 hour at 134e138 C by steam sterilization under pressure. Because it responds well to alkaline conditions, highly concentrated sodium hydroxide or phenol is used to decontaminate PrP Sc [22] .