A systems approach to prion disease.
Mol Syst Biol
; 5: 252, 2009.
Article
in En
| MEDLINE
| ID: mdl-19308092
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prion Diseases
/
Systems Biology
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Syst Biol
Journal subject:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Year:
2009
Document type:
Article
Affiliation country:
Estados Unidos