A systems approach to prion disease
SCIE
SCOPUS
- Title
- A systems approach to prion disease
- Authors
- Hwang, D; Lee, IY; Yoo, H; Gehlenborg, N; Cho, JH; Petritis, B; Baxter, D; Pitstick, R; Young, R; Spicer, D; Price, ND; Hohmann, JG; DeArmond, SJ; Carlson, GA; Hood, LE
- Date Issued
- 2009-03
- Publisher
- NATURE PUBLISHING GROUP
- Abstract
- Prions cause transmissible neurodegenerative diseases and replicate by conformational conversion of normal benign forms of prion protein (PrPC) to disease-causing PrPSc 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 PrPSc 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. Molecular Systems Biology 24 March 2009; doi: 10.1038/msb.2009.10
- Keywords
- microarray; network analysis; neurodegenerative disease; prion; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; QUANTITATIVE TRAIT LOCI; SCRAPIE-INFECTED MICE; SELECTIVE NEURONAL VULNERABILITY; CREUTZFELDT-JAKOB-DISEASE; CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; INCUBATION PERIOD; PRESYMPTOMATIC DETECTION; BENZODIAZEPINE-RECEPTOR
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/28439
- DOI
- 10.1038/MSB.2009.10
- ISSN
- 1744-4292
- Article Type
- Article
- Citation
- MOLECULAR SYSTEMS BIOLOGY, vol. 5, no. 252, page. 1 - 23, 2009-03
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.