LncRNA BDNF-AS promotes autophagy and apoptosis in MPTP-induced Parkinson's disease via ablating microRNA-125b-5p.

Recently, extensive evidence has indicated that the biological role of long non-coding RNAs (lncRNAs) in neurodegenerative diseases is becoming increasingly evident. The lncRNA brain-derived neurotrophic factor anti-sense (BDNF-AS) has been found to be dysregulated in Huntington's Disease. However, the function of BDNF-AS in Parkinson's disease (PD) remains unknown. The purpose of this present study was to explore the effect of BDNF-AS on PD and its underlying molecular mechanisms. The MPTP-induced mouse model of PD and MPP+-induced SH-SY5Y cell model were established. Immunofluorescence was performed to determine the number of TH + positive cells. Mice behavioral changes were detected by pole and rota-rod test. SH-SY5Y cells viability, apoptosis was detected by MTT assay and flow cytometry. The number of autophagosome was measured by transmission electron microscopy. Dopamine content was tested by high performance liquid chromatography. Dual-luciferase reporter gene assay was utilized to verify the correlation between BDNF-AS and miR-125b-5p. qRT-PCR and western blot were used to detect gene expression levels. Our results showed that BDNF-AS was up-regulated in MPTP-induced PD model and dopamine neurons, and MPP + treated SH-SY5Y cells, while miR-125b-5p was down-regulated. The expression of BDNF-AS was positively related with the MPP + concentration. BDNF-AS knockdown could significantly promote cell proliferation, while inhibit apoptosis and autophagy in SH-SY5Y cells treated by MPP + . Silencing BDNF-AS could also increase TH positive neurons and significantly suppress the autophagy of PD mice. Additionally, miR-125b-5p, a putative target gene of BDNF-AS, was involved in the effects of BDNF-AS on SH-SY5Y cell apoptosis and autophagy. Our study demonstrated that knockdown of BDNF-AS could elevate SH-SY5Y cell viability, inhibit autophagy and apoptosis in MPTP-induced PD models through regulating miR-125b-5p, suggesting that BDNF-AS might act as a potential therapeutic target for PD.

Fan Y ，Zhao X ，Lu K ，Cheng G ... -  《-》

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

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.

Dong LI ，Zheng Y ，Gao L ，Luo X ... -  《-》

lncRNA NEAT1 promotes autophagy of neurons in mice by impairing miR-107-5p.

Dong L ，Zheng Y ，Luo X 《-》

Knockdown of long non-coding RNA AL049437 mitigates MPP+ -induced neuronal injury in SH-SY5Y cells via the microRNA-205-5p/MAPK1 axis.

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. 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. 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. 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.

Zhang L ，Wang J ，Liu Q ，Xiao Z ，Dai Q ... -  《-》

SNHG1 promotes MPP(+)-induced cytotoxicity by regulating PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells via sponging miR-153-3p.

Zhao J ，Geng L ，Chen Y ，Wu C ... -  《-》