Xiang Guoliang, Wen Xueyi, Wang Wenjing, Peng Tianchan, Wang Jiazhen, Li Qinghua, Teng Junfang, Cui Ying
Department of Neurology Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541004, China.
Parkinsons Dis. 2023 Oct 12;2023:4422484. doi: 10.1155/2023/4422484. eCollection 2023.
Adenosine 5'-monophosphate-activated protein kinase ()'s effect in -induced kinase 1 () mutant Parkinson's disease (PD) transgenic flies and the related mechanism is seldom studied. The classic PD transgenic flies was utilized to generate the disease characteristics specifically expressed in flies' muscles, and Western blot (WB) was used to measure the expression of the activated form of to investigate whether activated alters in PD flies. was used to drive overexpression in flies to demonstrate the crucial role of in PD pathogenesis. The abnormal wing posture and climbing ability of PD transgenic flies were recorded. Mitochondrial morphology via transmission electron microscopy (TEM) and ATP and NADH: ubiquinone oxidoreductase core subunit S3 (NDUFS3) protein levels were tested to evaluate the alteration of the mitochondrial function in PD flies. Phosphorylated AMPK dropped significantly in flies compared to controls, and overexpression rescued flies' abnormal wing posture rate. The elevated dopaminergic neuron number in PPL1 via immunofluorescent staining was observed. Mitochondrial dysfunction in flies has been ameliorated with increased ATP level, restored mitochondrial morphology in muscle, and increased NDUFS3 protein expression. Conclusively, overexpression could partially rescue the PD flies via improving flies' mitochondrial function.
5'-单磷酸腺苷激活蛋白激酶（）在诱导激酶1（）突变型帕金森病（PD）转基因果蝇中的作用及其相关机制鲜有研究。利用经典的PD转基因果蝇在果蝇肌肉中特异性表达疾病特征，并采用蛋白质免疫印迹法（WB）检测激活形式的表达，以研究激活的在PD果蝇中是否发生改变。利用在果蝇中驱动过表达，以证明在PD发病机制中的关键作用。记录PD转基因果蝇异常的翅膀姿势和攀爬能力。通过透射电子显微镜（TEM）观察线粒体形态，并检测ATP和烟酰胺腺嘌呤二核苷酸：泛醌氧化还原酶核心亚基S3（NDUFS3）蛋白水平，以评估PD果蝇中线粒体功能的改变。与对照组相比，果蝇中磷酸化的AMPK显著下降，而过表达挽救了果蝇异常的翅膀姿势率。通过免疫荧光染色观察到PPL1中多巴胺能神经元数量增加。果蝇的线粒体功能障碍得到改善，ATP水平升高，肌肉中线粒体形态恢复，NDUFS3蛋白表达增加。总之，过表达可通过改善果蝇的线粒体功能部分挽救PD果蝇。
