Proteomics-based Development of Biomarkers for Prion Diseases

We analyzed the proteomic profile of ME7 scrapie-infected mouse brains, and the interactions and functions of selected differentially expressed proteins to identify potential new biomarkers to be applicable for the diagnosis of Prion diseases. Mice were intracerebrally inoculated with 10% homogenate of ME7 scrapie-infected mouse brains, and monitored for neurological symptoms. We screened for proteins specifically expressed in infected brain samples using one-dimensional gel electrophoresis and liquid chromatography-mass spectrometry. 317 proteins based on their peptide scores and ratio values were selected. The major biological processes identified were cellular and metabolic processes, localization, and transport. Selected proteins had functions related to neurological processes, including cell-cell signaling, transmission of nerve impulse, and synaptic transmission. We analyzed infected host cells using experimental and computational methods, and found many significant protein expression changes. We identified 43 candidate proteins with high peptide scores and ratio values. Of these, 36 potential candidate proteins were related to up regulated biological processes, and 7 to down regulated biological processes. We confirmed the presence of two of these differentially expressed candidate proteins using immunoblotting.