BACKGROUND Long noncoding RNAs (lncRNAs) have been defined as critical regulators of various human diseases. However, the functions of lncRNAs in Parkinson's disease (PD) have not yet been elucidated. In this study, we investigated the role of lncRNA AL049437 in PD and its underlying mechanism. METHODS An in vivo model of PD was established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), while an in vitro model was created using N-methyl-4-phenylpyridinium (MPP+). Gene expression was evaluated using quantitative reverse transcriptase polymerase chain reaction and western blotting. The effects and mechanism of AL049437 in PD were explored using Cell Counting Kit-8 assay, flow cytometry, enzyme-linked immunosorbent assay, and 2',7'-dichlorodihydrofluorescein diacetate fluorescence assay. The interaction between AL049437, miR-205-5p, and mitogen-activated protein kinase 1 (MAPK1) was evaluated using luciferase reporter and RNA pull-down assays. RESULTS The expression of AL049437 was upregulated, while that of miR-205-5p was downregulated in MPTP-induced PD mouse model and MPP+-treated SH-SY5Y cells. Silencing of AL049437 mitigated MPP+-induced neurotoxicity in SH-SY5Y cells, as demonstrated by increased cell viability and reduced cell apoptosis. Furthermore, silencing of AL049437 alleviated MPP+-induced neuroinflammation and oxidative stress, as indicated by the reduction in tumor necrosis factor-α and interleukin-6 levels and reactive oxygen species production. In addition, AL049437 was predominantly localized in the cytoplasm of SH-SY5Y cells and functioned as an miR-205-5p sponge. Moreover, MAPK1 was identified as a downstream target of miR-205-5p. Remarkably, the impact of AL049437 silencing on MPP+-induced neuronal damage could be blocked by miR-205-5p inhibition or MAPK1 overexpression. CONCLUSION Knockdown of lncRNA AL049437 mitigates MPP+ -induced neuronal injury in SH-SY5Y cells by regulating the miR-205-5p/MAPK1 axis. Our research reveals a novel regulatory mechanism of AL049437 in PD progression.

中文翻译：

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敲低长的非编码RNA AL049437可以通过microRNA-205-5p / MAPK1轴减轻MPP +诱导的SH-SY5Y细胞神经元损伤。

背景技术长非编码RNA（lncRNA）已经被定义为各种人类疾病的关键调节剂。但是，lncRNA在帕金森氏病（PD）中的功能尚未阐明。在这项研究中，我们调查了lncRNA AL049437在PD中的作用及其潜在机制。方法采用1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）建立PD的体内模型，而采用N-甲基-4-苯基吡啶（MPP +）建立体外模型。使用定量逆转录酶聚合酶链反应和蛋白质印迹评估基因表达。使用细胞计数试剂盒8检测，流式细胞仪，酶联免疫吸附测定和2'，7'-二氯二氢荧光素二乙酸酯荧光测定法探索AL049437在PD中的作用和机制。AL049437之间的交互，使用荧光素酶报道分子和RNA下拉测定法评估了miR-205-5p和促分裂原活化蛋白激酶1（MAPK1）。结果在MPTP诱导的PD小鼠模型和MPP +处理的SH-SY5Y细胞中，AL049437的表达上调，而miR-205-5p的表达下调。AL049437的沉默减轻了SH-SY5Y细胞中MPP +诱导的神经毒性，这可以通过增加细胞活力和减少细胞凋亡来证明。此外，AL049437的沉默减轻了MPP +诱导的神经炎症和氧化应激，如肿瘤坏死因子-α和白介素6水平的降低以及活性氧的产生所表明的。此外，AL049437主要位于SH-SY5Y细胞的细胞质中，并起着miR-205-5p海绵的作用。此外，MAPK1被确定为miR-205-5p的下游目标。值得注意的是 miR-205-5p抑制或MAPK1过表达可阻止AL049437沉默对MPP +诱导的神经元损伤的影响。结论敲低lncRNA AL049437可通过调节miR-205-5p / MAPK1轴减轻MPP +诱导的SH-SY5Y细胞神经元损伤。我们的研究揭示了AL049437在PD进展中的新型调节机制。