Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: April 20, 2010
Publication Date: N/A
Technical Abstract: Prions are novel pathogens that cause a set of rare fatal neurological diseases know as transmissible spongiform encephalopathies. Examples of these diseases include Creutzfeldt-Jakob disease, scrapie and chronic wasting disease. Prions are able to recruit a normal cellular prion protein and convert it into a prion and thereby propagate an infection. Unlike other pathogens, the information necessary to propagate the infection is contained in the conformation of the protein comprising the prion isoform and not in nucleic acids. Prions and the normal cellular prion protein isoform have different physicochemical properties although they possess identical covalent structures. We exploit ultracentrifugation to isolate infectious prions and analyze them by mass spectrometry. This approach works on both proteinase K resistant and sensitive forms of prions. We use a nano LC-MS-MS system to quantitate the prions present in a sample. Our limit of detection is in the attomole range (10(-18)mole). Oxidation of methionine has been proposed to be important in prion formation. Using mass spectrometry, we assessed the role of methionine oxidation in prion propagation in hamsters. We have used mass spectrometry to quantitate prions and determine the role of specific amino acids in the pathology of prions.