Patients with Parkinson's disease (PD) show a common progressive neurodegenerative movement disorder characterized by rigidity, tremors, postural instability, and bradykinesia due to the loss of dopaminergic neurons in the substantia nigra, and is often accompanied by several non-motor symptoms, called parkinsonism. Several lines of recent evidence support the hypothesis that mutations in the gene encoding phosphoglycerate kinase (PGK) play an important role in the PD mechanism. PGK is a key enzyme in the glycolytic pathway that catalyzes the reaction from 1,3-diphosphoglycerate to 3-phosphoglycerate. We herein established a parkinsonism model targeting Drosophila Pgk. Dopaminergic (DA) neuron-specific Pgk knockdown lead to locomotive defects in both young and aged adult flies and was accompanied by progressive DA neuron loss with aging. Pgk knockdown in DA neurons decreased dopamine levels in the central nervous system (CNS) of both young and aged adult flies. These phenotypes are similar to the defects observed in human PD patients, suggesting that the Pgk knockdown flies established herein are a promising model for parkinsonism. Furthermore, pan-neuron-specific Pgk knockdown induced low ATP levels and the accumulation of reactive oxygen species (ROS) in the CNS of third instar larvae. Collectively, these results indicate that a failure in the energy production system of Pgk knockdown flies causes locomotive defects accompanied by neuronal dysfunction and degeneration in DA neurons.

帕金森病 (PD) 患者表现出一种常见的进行性神经退行性运动障碍，其特征是由于黑质中多巴胺能神经元的丧失而导致的僵硬、震颤、姿势不稳定和运动迟缓，并且通常伴有几种非运动症状，称为帕金森症. 最近的几条证据支持这样一种假设，即编码磷酸甘油酸激酶 (PGK) 的基因突变在 PD 机制中起重要作用。PGK 是糖酵解途径中的关键酶，可催化 1,3-二磷酸甘油酸到 3-磷酸甘油酸的反应。我们在此建立了一个针对果蝇 Pgk的帕金森症模型。多巴胺能 (DA) 神经元特异性Pgk击倒导致年轻和年老的成年果蝇的运动缺陷，并伴随着随着年龄的增长而进行性 DA 神经元丢失。DA 神经元中的Pgk敲低降低了年轻和老年成年果蝇的中枢神经系统 (CNS) 中的多巴胺水平。这些表型类似于在人类 PD 患者中观察到的缺陷，表明本文建立的Pgk敲低果蝇是帕金森病的有希望的模型。此外，泛神经元特异性Pgk敲低诱导低 ATP 水平和活性氧 (ROS) 在三龄幼虫的 CNS 中的积累。总的来说，这些结果表明Pgk的能源生产系统出现故障 击倒果蝇会导致运动缺陷，并伴有神经元功能障碍和 DA 神经元的退化。