Abstract
The goal of the present study was to elucidate the mechanism by which long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) promotes inflammation in Parkinson’s disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce PD development in C57BL/6 mice, and tyrosine hydroxylase (TH) expression was analysed by immunohistochemical analysis. Western blot and qPCR analyses were conducted to assess the expression of protein and mRNA levels, respectively. Lipopolysaccharide/adenosine triphosphate (LPS/ATP) was used to activate microglia in vitro. Chromatin immunoprecipitation (ChIP), RNA pull-down and RNA immunoprecipitation chip (RIP) assays were performed to investigate the interaction among specific molecules. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cell viability and proliferation. Flow cytometry was performed to analyse cell apoptosis after staining. The dichlorofluorescein diacetate (DCFH-DA) assay was used to measure the generation of reactive oxygen species (ROS) in cells. The results showed that MALAT1 was highly expressed in the brains of MPTP-induced PD model mice and in LPS/ATP-induced microglia cells. Knockdown of MALAT1 inhibited elevated nuclear factor (erythroid-derived 2)-like-2 factor (NRF2) expression, thereby inhibiting inflammasome activation and ROS production. MALAT1 was shown to promote neuroinflammation by recruiting enhancer of zeste homologue 2 (EZH2) to the promoter of NRF2, suppressing Nrf2 expression. In summary, MALAT1 epigenetically inhibits NRF2, thereby inducing inflammasome activation and reactive oxygen species (ROS) production in PD mouse and microglial cell models.
Highlights
Parkinson’s disease (PD) is an age-related degenerative disorder of the nervous system that affects the movement abilities of adults [1]
Expressed Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and suppressed Nuclear factor (erythroid-derived 2)-like-2 factor (Nrf2) are coupled with inflammasome activation in the brain of PD mice Mouse PD models (n = 8) were established by intraperitoneally injecting mice with MPTP, and mice treated with 0.9% sterile saline solution were used as the control group (n = 6)
Activation of microglia in the brains of PD mice was significantly increased compared with that observed in the control group by assessing the Knockdown of MALAT1 attenuates inflammasome activation induced by LPS/Lipopolysaccharide/adenosine triphosphate (ATP) treatment in BV2 cells we investigated the effect of MALAT1 knockdown on inflammasome activation in BV2 cells
Summary
Parkinson’s disease (PD) is an age-related degenerative disorder of the nervous system that affects the movement abilities of adults [1]. Cai et al Molecular Brain (2020) 13:130 activated in LPS- and 6-hydroxydopamine hydrobromide (6-OHDA)-induced PD rats [6]. In the central nervous system, the NLRP3 inflammasome signalling pathway plays a crucial role in neuroinflammatory processes, such as neurodegenerative diseases. Sarkar et al recently demonstrated that amplification of NLRP3 inflammasome activation by mitochondrial impairment in microglia promotes the development of PD [7]. There is an urgent need to understand the pathogenic mechanism of PD at the molecular level and identify potential targets to develop novel therapeutic strategies for this disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
