What can Drosophila tell us about serpins, thrombosis and dementia?
The validity of the fruit-fly as a model of human disease has been confirmed in a striking way by Green and colleagues.1 They show that the mutations causing a necrotic disease phenotype in Drosophila, precisely mirror those resulting in a group of well-studied but perplexing diseases in the human. These diseases, ranging from thrombosis to dementia, arise from mutations causing a conformational instability of serpin protease inhibitors. The findings provide clues as to the unusual severity and variable onset of such conformational diseases and demonstrate the potential of Drosophila as a model for their future study.
Carrell
Robin
R
University of Cambridge, Cambridge Institute of Medical Research, Cambridge, UK. rwc1000@cam.ac.uk
Corral
Javier
J
D000818:Animals; D030801:Animals, Genetically Modified; D003704:Dementia / Q000235:genetics; D004330:Drosophila / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D011480:Protease Inhibitors / Q000494:pharmacology; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D015843:Serpins / Q000737:chemistry; D013927:Thrombosis / Q000235:genetics
D011480:Protease Inhibitors; D015843:Serpins