RRC ID 11925
Author Pandey UB, Nichols CD.
Title Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery.
Journal Pharmacol. Rev.
Abstract The common fruit fly, Drosophila melanogaster, is a well studied and highly tractable genetic model organism for understanding molecular mechanisms of human diseases. Many basic biological, physiological, and neurological properties are conserved between mammals and D. melanogaster, and nearly 75% of human disease-causing genes are believed to have a functional homolog in the fly. In the discovery process for therapeutics, traditional approaches employ high-throughput screening for small molecules that is based primarily on in vitro cell culture, enzymatic assays, or receptor binding assays. The majority of positive hits identified through these types of in vitro screens, unfortunately, are found to be ineffective and/or toxic in subsequent validation experiments in whole-animal models. New tools and platforms are needed in the discovery arena to overcome these limitations. The incorporation of D. melanogaster into the therapeutic discovery process holds tremendous promise for an enhanced rate of discovery of higher quality leads. D. melanogaster models of human diseases provide several unique features such as powerful genetics, highly conserved disease pathways, and very low comparative costs. The fly can effectively be used for low- to high-throughput drug screens as well as in target discovery. Here, we review the basic biology of the fly and discuss models of human diseases and opportunities for therapeutic discovery for central nervous system disorders, inflammatory disorders, cardiovascular disease, cancer, and diabetes. We also provide information and resources for those interested in pursuing fly models of human disease, as well as those interested in using D. melanogaster in the drug discovery process.
Volume 63(2)
Pages 411-36
Published 2011-6
DOI 10.1124/pr.110.003293
PII pr.110.003293
PMID 21415126
PMC PMC3082451
MeSH Animals Disease Models, Animal* Drosophila melanogaster / genetics Drosophila melanogaster / physiology* Drug Delivery Systems Drug Design Drug Discovery / methods* High-Throughput Screening Assays / methods Humans Species Specificity
IF 18.964
Times Cited 198