2009/03/24 by Daehee Hwang, Inyoul Y. Lee, Hyuntae Yoo +12 · 294 citations
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Prion Diseases and Protein Misfolding #RNA Research and Splicing #Neurological diseases and metabolism #Library science #Biology #Computer science
paper · pdf · doi:10.1038/msb.2009.10
published in Molecular Systems Biology 5(1), 252 (Springer Nature)
openalex publication_date 2009/03/24 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Prions cause transmissible neurodegenerative diseases and replicate by conformational conversion of normal benign forms of prion protein (PrP(C)) to disease-causing PrP(Sc) isoforms. A systems approach to disease postulates that disease arises from perturbation of biological networks in the relevant organ. We tracked global gene expression in the brains of eight distinct mouse strain-prion strain combinations throughout the progression of the disease to capture the effects of prion strain, host genetics, and PrP concentration on disease incubation time. Subtractive analyses exploiting various aspects of prion biology and infection identified a core of 333 differentially expressed genes (DEGs) that appeared central to prion disease. DEGs were mapped into functional pathways and networks reflecting defined neuropathological events and PrP(Sc) replication and accumulation, enabling the identification of novel modules and modules that may be involved in genetic effects on incubation time and in prion strain specificity. Our systems analysis provides a comprehensive basis for developing models for prion replication and disease, and suggests some possible therapeutic approaches.