AI Article Synopsis
- Increasing evidence suggests that neuroinflammation plays a role in the progression of Parkinson's disease (PD), with long noncoding RNAs (lncRNAs) significantly impacting inflammatory processes in various diseases.
- The study focused on lncRNA KCNQ1OT1, finding that its knockdown reduced microglial NLRP3 inflammasome activation and decreased dopaminergic neuronal loss in PD model mice.
- KCNQ1OT1 functions by binding with miR-186 to promote inflammasome activation and inhibit its silencing, revealing a new regulatory network that could inform future treatments for Parkinson's disease.
Article Abstract
Increasing evidence indicated that neuroinflammation was involved in progression of Parkinson's disease (PD). Long noncoding RNAs (lncRNAs) played important roles in regulating inflammatory processes in multiple kinds of human diseases such as cancer diabetes, cardiomyopathy, and neurodegenerative disorders. The mechanisms by which lncRNAs regulated PD related inflammation and dopaminergic neuronal loss have not yet been fully elucidated. In current study, we intended to explore the function and potential mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in regulating inflammasome activation in PD. Functional assays confirmed that knockdown of KCNQ1OT1 suppress microglial NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and attenuated dopaminergic neuronal loss in PD model mice. As KCNQ1OT1 located in both cytoplasm and nucleus of microglia, we demonstrated that KCNQ1OT1 promoted microglial NLRP3 inflammasome activation by competitive binding with miR-186 in cytoplasm and inhibited pri-miR-186 mediated NLRP3 silencing through recruitment of DiGeorge syndrome critical region gene 8 (DGCR8) in nucleus, respectively. Our study found a novel lncRNA-pri-miRNA/mature miRNA-mRNA regulatory network in microglia mediated NLRP3 inflammasome activation and dopaminergic neuronal loss, provided further insights for the treatment of Parkinson's disease.
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| http://dx.doi.org/10.1016/j.bbadis.2024.167454 | DOI Listing |
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