論文 - 詳細
| RRC ID | 359 |
|---|---|
| 著者 | Agrawal N, Pallos J, Slepko N, Apostol BL, Bodai L, Chang LW, Chiang AS, Thompson LM, Marsh JL. |
| タイトル | Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
We explore the hypothesis that pathology of Huntington's disease involves multiple cellular mechanisms whose contributions to disease are incrementally additive or synergistic. We provide evidence that the photoreceptor neuron degeneration seen in flies expressing mutant human huntingtin correlates with widespread degenerative events in the Drosophila CNS. We use a Drosophila Huntington's disease model to establish dose regimens and protocols to assess the effectiveness of drug combinations used at low threshold concentrations. These proof of principle studies identify at least two potential combinatorial treatment options and illustrate a rapid and cost-effective paradigm for testing and optimizing combinatorial drug therapies while reducing side effects for patients with neurodegenerative disease. The potential for using prescreening in Drosophila to inform combinatorial therapies that are most likely to be effective for testing in mammals is discussed. |
| 巻・号 | 102(10) |
| ページ | 3777-81 |
| 公開日 | 2005-3-8 |
| DOI | 10.1073/pnas.0500055102 |
| PII | 0500055102 |
| PMID | 15716359 |
| PMC | PMC553288 |
| MeSH | Amides / administration & dosage Animals Benzoquinones Disease Models, Animal* Drosophila Drug Therapy, Combination Female Huntington Disease / drug therapy* Hydroxamic Acids / administration & dosage Lactams, Macrocyclic Nerve Degeneration / prevention & control Nerve Tissue Proteins / genetics* Nuclear Proteins / genetics* Pyridines / administration & dosage Quinones / administration & dosage Vorinostat |
| IF | 9.412 |
| 引用数 | 119 |
| WOS 分野 | NEUROSCIENCES |
| リソース情報 | |
| ショウジョウバエ | |