IncRNA NEAT1 prompts autophagy and apoptosis in MPTP-induced Parkinson's disease by impairing miR-374c-5p

• 作者: Li Dong Yumin Zheng Lianbo Gao Xiaoguang Luo
• 来源期刊: 生物化学与生物物理学报（英文版）
• 年，卷（期）: 2021,（7）
• 所属期刊栏目: Original Articles
• 页码范围: 870-882
• 页数: 13页
• 语种: 英文
• DOI: 10.1093/abbs/gmab055

摘要

Long non-coding RNAs (IncRNAs) play biological roles in brain disorder and neurodegenerative diseases.As the functions of IncRNA NEAT1 in Parkinson's disease (PD) remain unknown,in the present study,we aimed to explore the roles and underlying molecular mechanisms of NEAT1 in PD.A PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and a cell model of SH-SY5Y induced by N-methyl-4-phenylpyridinium (MPP+) were established.The ratio of tyrosine hydroxylase (TH+) cells was determined by immunofluorescence assay,and the behavioral changes in mice were observed using pole tests and rotarod tests.The cellular viability and apoptosis of SH-SY5Y were detected by MTT assay and flow cytometric analysis,respectively,and the number of autophagosomes was subsequently measured by transmission electron microscopy.High-performance liquid chromatography was performed to detect the con-tent of dopamine,and a dual-luciferase reporter assay was used to clarify the target of NEAT1 simultaneously.The results demonstrated that the level of NEAT1 was upregulated in the MPTP-induced PD mice,dopamine neurons,and the SH-SY5Y cells treated with MPP+,whereas the level of miR-374c-5p was downregulated.NEAT1 level was positively correlated with MPP+ in a concentration-dependent manner.NEAT1 inhibition efficiently facilitated cell proliferation but inhibited apoptosis and autophagy in the MPP+-treated SH-SY5Y cells.Additionally,silencing of NEAT1 increased the TH+ rate of neurons and suppressed autophagy greatly in PD mice.As a pos-sible target of NEAT1,miR-374c-5p could impact on the apoptosis and autophagy of the SH-SY5Y cells.NEAT1 inhibition upregulated the expression of miR-374c-5p,enhanced SH-SY5Y cell viabil-ity,and repressed autophagy and apoptosis in MPTP-induced PD mice.These findings indicated a potential therapeutic role of NEAT1 in treating PD.