lncRNA 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 

机构地区：[1]Department of Neurology,The Fourth Affiliated Hospital of China Medical University,Shenyang 110032,China [2]Department of Neurology,The First Affiliated Hospital of China Medical University,Shenyang 110000,China [3]Department of Neurology,The First Affiliated Hospital of South University of Science and Technology,The Second Clinical Medical College of Jinan University,Shenzhen People’s Hospital,Shenzhen 518000,China

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第7期870-882,共13页生物化学与生物物理学报（英文版）

基　　金：This work is supported by the grant from the National Natural Science Foundation of China(No.81771375).

摘　　要：Long non-coding RNAs(lncRNAs)play biological roles in brain disorder and neurodegenerative diseases.As the functions of lncRNA 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 content 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 possible 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 viability,and repressed autophagy and apoptosis in MPTP-induced PD mice.These findings indicated a potential therapeutic role of NEAT1 in treating PD.

关 键 词：Parkinson’s disease AUTOPHAGY APOPTOSIS NEAT1 miR-374c-5p 

分 类 号：R742.5[医药卫生—神经病学与精神病学]