Parkinson's disease (PD) is a progressive neurodegenerative disorder with increasing prevalence in elderly individuals globally. MicroRNAs (miRNAs) have been confirmed to participate in the pathogenesis of various neurodegenerative diseases, including PD. MiR-497-5p is previously reported to be upregulated in PD. The present study was designed to further explore the function of miR-497-5p in PD. MiR-497-5p was significantly upregulated in 1-methyl-4-phenylpyridinium (MPP⁺)-treated SH-SY5Y cells. Inhibition of miR-497-5p suppressed the cell apoptosis and triggered autophagy of MPP⁺-treated SH-SY5Y cells. Further, miR-497-5p targeted fibroblast growth factor-2 (FGF2) in MPP⁺-treated SH-SY5Y cells. Subsequently, rescue assays revealed that miR-497-5p regulated apoptosis and autophagy of MPP⁺-treated SH-SY5Y cells by mediation on FGF2. In addition, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mice models were established. The results exhibited that silencing of miR-497-5p improved mice bradykinesia, reduced cell apoptosis and induced autophagy in PD mice by FGF2. In conclusion, silencing of miR-497-5p alleviates PD by suppressing cell apoptosis and promoting autophagy in a FGF2 dependent manner, which will provide a novel target for Parkinson's disease management.

中文翻译：

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沉默 miR-497-5p 通过上调 FGF2 抑制细胞凋亡并促进帕金森病中的自噬

帕金森病 (PD) 是一种进行性神经退行性疾病，在全球老年人中的患病率越来越高。MicroRNAs (miRNAs) 已被证实参与包括 PD 在内的多种神经退行性疾病的发病机制。此前有报道称 MiR-497-5p 在 PD 中上调。本研究旨在进一步探索 miR-497-5p 在 PD 中的功能。MiR-497-5p 在 1-甲基-4-苯基吡啶鎓 (MPP ⁺ ) 处理的 SH-SY5Y 细胞中显着上调。抑制 miR-497-5p 可抑制细胞凋亡并引发 MPP ⁺处理的 SH-SY5Y 细胞的自噬。^{此外，miR-497-5p 靶向 MPP +}中的成纤维细胞生长因子 2 (FGF2)-处理的 SH-SY5Y 细胞。随后，拯救分析显示，miR-497-5p 通过介导 FGF2 调节 MPP ⁺处理的 SH-SY5Y 细胞的凋亡和自噬。此外，建立了1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的PD小鼠模型。结果表明，miR-497-5p 的沉默改善了小鼠运动迟缓，减少了 FGF2 在 PD 小鼠中的细胞凋亡和诱导自噬。总之，沉默 miR-497-5p 通过抑制细胞凋亡和以 FGF2 依赖性方式促进自噬来缓解 PD，这将为帕金森病管理提供新的靶点。