Department of Neurology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Cardiology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Environ Toxicol. 2021 Nov;36(11):2302-2312. doi: 10.1002/tox.23344. Epub 2021 Aug 29.
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.
帕金森病(PD)是一种进行性神经退行性疾病,在全球老年人群中的发病率不断上升。microRNAs(miRNAs)已被证实参与了多种神经退行性疾病的发病机制,包括 PD。先前有报道称 miR-497-5p 在 PD 中上调。本研究旨在进一步探讨 miR-497-5p 在 PD 中的作用。miR-497-5p 在 1-甲基-4-苯基吡啶(MPP)处理的 SH-SY5Y 细胞中显著上调。抑制 miR-497-5p 可抑制 MPP 处理的 SH-SY5Y 细胞的细胞凋亡并触发自噬。此外,miR-497-5p 在 MPP 处理的 SH-SY5Y 细胞中靶向成纤维细胞生长因子-2(FGF2)。随后,挽救实验表明,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 的沉默通过 FGF2 改善了 PD 小鼠的运动迟缓,减少了细胞凋亡并诱导了 PD 小鼠的自噬。总之,通过依赖于 FGF2 的方式抑制细胞凋亡和促进自噬,沉默 miR-497-5p 可减轻 PD,为帕金森病的管理提供了新的靶点。