Department of Biology, University of Padova, 35131 Padova, Italy.
Cognitive Neuroscience Center, University of Padova, 35100 Padova, Italy.
Int J Mol Sci. 2018 Dec 6;19(12):3911. doi: 10.3390/ijms19123911.
Clinical and research studies have suggested a link between Parkinson's disease (PD) and alterations in the circadian clock. may represent a useful model to study the relationship between the circadian clock and PD. Apart from the conservation of many genes, cellular mechanisms, signaling pathways, and neuronal processes, shows an organized central nervous system and well-characterized complex behavioral phenotypes. In fact, has been successfully used in the dissection of the circadian system and as a model for neurodegenerative disorders, including PD. Here, we describe the fly circadian and dopaminergic systems and report recent studies which indicate the presence of circadian abnormalities in some fly PD genetic models. We discuss the use of to investigate whether, in adults, the disruption of the circadian system might be causative of brain neurodegeneration. We also consider approaches using , which might provide new information on the link between PD and the circadian clock. As a corollary, since PD develops its symptomatology over a large part of the organism's lifespan and given the relatively short lifespan of fruit flies, we suggest that genetic models of PD could be used to perform lifelong screens for drug-modulators of general and/or circadian-related PD traits.
临床和研究表明，帕金森病（PD）与生物钟的变化有关。果蝇可能是研究生物钟与 PD 关系的有用模型。除了许多基因、细胞机制、信号通路和神经元过程的保守性外，果蝇还表现出有组织的中枢神经系统和特征明确的复杂行为表型。事实上，果蝇已成功用于解析生物钟系统，并作为包括 PD 在内的神经退行性疾病的模型。在这里，我们描述了果蝇的生物钟和多巴胺能系统，并报告了最近的研究表明，一些果蝇 PD 遗传模型存在生物钟异常。我们讨论了使用果蝇来研究在成年期，生物钟系统的破坏是否可能是大脑神经退行性变的原因。我们还考虑了使用 的方法，这可能为 PD 与生物钟之间的联系提供新的信息。因此，由于 PD 在生物体寿命的很大一部分时间内发展其症状，并且鉴于果蝇的寿命相对较短，我们建议可以使用 PD 的遗传模型来对一般和/或与生物钟相关的 PD 特征的药物调节剂进行终生筛选。
