Haywood Annika F M, Staveley Brian E
Department of Biology, Memorical University of Newfoundland, St. John's, Canada.
Genome. 2006 May;49(5):505-10. doi: 10.1139/g06-011.
Parkinson's disease (PD) patients show a characteristic loss of motor control caused by the degeneration of dopaminergic neurons. Mutations in the genes that encode alpha-synuclein and parkin have been linked to inherited forms of this disease. The parkin protein functions as a ubiquitin ligase that targets proteins for degradation. Expression of isoforms of human alpha-synuclein in the Drosophila melanogaster nervous system forms the basis of an excellent genetic model that recapitulates phenotypic and behavioural features of PD. Using this model, we analysed the effect of parkin co-expression on the climbing ability of aging flies, their life span, and their retinal degeneration. We have determined that co-expression of parkin can suppress phenotypes caused by expression of mutant alpha-synuclein. In the developing eye, parkin reduces retinal degeneration. When co-expressed in the dopaminergic neurons, the ability to climb is extended over time. If conserved in humans, we suggest that upregulation of parkin may prove a method of suppression for PD induced by mutant forms of alpha-synuclein.
帕金森病（PD）患者表现出由多巴胺能神经元退化导致的特征性运动控制丧失。编码α-突触核蛋白和帕金蛋白的基因突变与这种疾病的遗传形式有关。帕金蛋白作为一种泛素连接酶，靶向蛋白质进行降解。在果蝇神经系统中表达人α-突触核蛋白的异构体构成了一个出色的遗传模型的基础，该模型概括了帕金森病的表型和行为特征。利用这个模型，我们分析了共表达帕金蛋白对衰老果蝇攀爬能力、寿命及其视网膜退化的影响。我们已经确定，帕金蛋白的共表达可以抑制由突变型α-突触核蛋白表达引起的表型。在发育中的眼睛中，帕金蛋白可减少视网膜退化。当在多巴胺能神经元中共表达时，攀爬能力会随着时间的推移而延长。如果在人类中也存在这种保守性，我们认为上调帕金蛋白可能是一种抑制由突变型α-突触核蛋白诱导的帕金森病的方法。
