Biology

A Systems Approach to Prion Diseases
Daehee Hwang, Pohang University of Science and Technology (POSTECH)

Prions replicate by conformational conversion of benign prion protein (PrPC) to pathogenic PrPSc isoforms, causing transmissible neurodegenerative diseases. A systems approach postulates that disease arises from perturbation of biological networks. We tracked time-course gene expression profiles in the brains of eight different mouse–prion strain combinations throughout the disease progression. Integrative analyses of these data identified a core of 333 differentially expressed genes (DEGs) that appeared central to prion disease. Mapping these core genes to cellular processes and pathways revealed a serial activation of cellular processes and their transition along the disease progression. Protein-protein interaction networks revealed close interactions among the early and late processes during the course of the disease progression. Transcriptional regulatory networks further revealed key regulatory mechanisms underlying dynamic activation of the cellular processes. Our systems analysis provides comprehensive resources for developing models for prion pathogenesis and suggests some possible diagnostic and therapeutic approaches.

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