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Selected publications
Prions are unconventional infectious pathogens that cause a variety of fatal neurodegenerative diseases in hosts. Prion diseases include Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and chronic wasting disease (CWD) in deer and elks. Although its unique property as a pathogen has been a subject of controversial debates since the discovery of the prion, the nature of the pathogen distinguishes prion from other conventional pathogens such as fungi, bacteria and viruses. To our current understanding, t he mode of prion propagation has become one of the paradigms that represent novel pathophysiological phenomena.
Prions are composed of protein termed PrP Sc that is devoid of nucleic acids. This disease-associated PrP Sc is a post-translationally misfolded isoform of PrP C encoded on PRNP gene locus and abundantly expressed in neurons. Despite the physiological role of PrP C has not been fully understood, expression of PrP C is tightly associated to the development of diseases. During prion pathogenesis, PrP Sc (disease-associated rogue PrP) recruits and converts PrP C (cellular PrP with normal physiological function) to form nascent PrP Sc. When PrP C is converted to PrP Sc, it undergoes a major biochemical alteration from an a-helical to a ß-sheet conformation. The switch of PrP C to PrP Sc requires the assistance of an auxiliary factor (provisionally designated protein X) that interacts with PrP C. Despite the numerous investigations searching for protein X, the molecular identity of protein X is still not evident.
Our long term goal of research is the understanding of the molecular mechanism of prion pathogenesis. This includes the understanding of molecular events during PrP C conversion to PrP Sc and biochemical alterations associated with prion infection and disease progression in the levels of cells and tissues.
Although recent experimental data advances our knowledge about the agent's ability to cross species barriers and options for detection and removal of the agent in addition to the nature of the agent, a majority of information about the molecular mechanism of prion propagation has not been clearly revealed. Thus, having the idea that protein X functions in the process of prion conversion, our primary interest and effort are focused on identifying protein X and understanding its interaction with PrP C for the conversion to PrP Sc.
Specifically, we have identified a group of candidate molecules for protein X using molecular biological means and biochemically characterized their binding properties to PrP C. With a reverse genetic approach, we verify their roles as protein X by testing whether the molecules functionally assist the molecular conversion of prion protein during pathogenesis. Other research projects are the investigations on 1) a physiological role of the interaction between PrP and its interacting proteins, 2) biochemical/cellular events that accompany with prion infection or result in disease progression, and 3) prion diagnostics and therapeutics.