Inhibition of foxo and minibrain in Dopaminergic Neurons Can Model Aspects of Parkinson Disease in Drosophila melanogaster
Inhibition of foxo and minibrain in Dopaminergic Neurons Can Model Aspects of Parkinson Disease in Drosophila melanogaster作者机构：Department of Biology Memorial University of Newfoundland St. John’s Newfoundland & Labrador Canada
出 版 物：《Advances in Parkinson's Disease》 (帕金森（英文）)
年 卷 期：2016年第5卷第1期
页 面：1-6页
主 题：Drosophila melanogaster Model of Parkinson Disease foxo minibrain
摘 要：Symptoms of Parkinson Disease (PD), the second most common neurodegenerative disease, emerge due to degeneration of dopaminergic neurons. Recently, a genome wide study revealed a role for a foxo transcription factor in PD. In the model organism Drosophila melanogaster, we have attempted 1) to inhibit the sole Drosophila homologue of foxo through the directed expression of a stable inducible RNAi transgene and 2) to indirectly increase foxo transcription activity through the inhibition of the kinase minibrain (mnb), a foxo transcriptional inhibitor. To evaluate the lifetime consequences upon the flies, longevity assays and locomotion over time assays were conducted. The inhibition of foxo by foxo-RNAi decreases life span significantly when expressed under the control of Tyrosine Hydroxylase-Gal4 (TH-Gal4). The targeted expression of mnb-RNAi, in the dopaminergic neurons, with an expected loss of suppression of foxo transcriptional activity, results in a significant loss of climbing ability. Thus alteration of foxo activity, both by RNA-inhibition and by down-regulation of an inhibitor of foxo, minibrain, produces novel Drosophila models of Parkinson Disease.
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