Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, Guangxi 541004, China.
Clinical Research Center for Neurological Diseases of Guangxi Province, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China.
Neurosci Lett. 2024 Sep 14;839:137917. doi: 10.1016/j.neulet.2024.137917. Epub 2024 Aug 3.
PTEN-induced kinase1 (PINK1) mutation is the main cause of autosomal recessive inheritance and early-onset Parkinson's disease. Mitochondrial respiratory chain complex I (CI) functional impairment has been considered to be an important factor in the pathogenesis of PD in recent years. In addition, NDUFS3 (nicotinamide adenine dinucleotide deoxylase iron-thionein 3) is one of the core subunits of mitochondrial CI. Therefore, this study explored the role of NDUFS3 gene in PINK1 transgenic Drosophila and its possible related mechanisms. In this study, the PD transgenic Drosophila model of MHC-Gal4/UAS system was selected to specifically activate the expression of PINK1 gene in the chest muscle tissue of Drosophila melanogaster. NDUFS3 RNAi interference was used to interfere with PINK1 transgenic Drosophila melanogaster and its effect on PD transgenic flies was studied. The results suggest that down-regulation of NDUFS3 gene expression may have a protective effect on PINK1 transgenic Drosophila melanogaster, and we speculate that down-regulation of NDUFS3 gene expression to reduce oxidative stress and restore mitochondrial function may be related to mitochondrial stress response.
PTEN 诱导激酶 1（PINK1）突变是常染色体隐性遗传和早发性帕金森病的主要原因。近年来，线粒体呼吸链复合物 I（CI）功能障碍被认为是 PD 发病机制中的一个重要因素。此外，NDUFS3（烟酰胺腺嘌呤二核苷酸脱氢酶铁硫蛋白 3）是线粒体 CI 的核心亚基之一。因此，本研究探讨了 NDUFS3 基因在 PINK1 转基因果蝇中的作用及其可能的相关机制。本研究选择 MHC-Gal4/UAS 系统的 PD 转基因果蝇模型，特异性激活黑腹果蝇胸部肌肉组织中 PINK1 基因的表达。使用 NDUFS3 RNAi 干扰来干扰 PINK1 转基因果蝇，并研究其对 PD 转基因果蝇的影响。结果表明，下调 NDUFS3 基因表达可能对 PINK1 转基因果蝇具有保护作用，我们推测下调 NDUFS3 基因表达以减轻氧化应激和恢复线粒体功能可能与线粒体应激反应有关。
