越来越多的证据表明神经炎症与帕金森病（PD）的进展有关。长链非编码RNA（lncRNA）在多种人类疾病（如癌症、糖尿病、心肌病和神经退行性疾病）的炎症过程调节中发挥着重要作用。 lncRNA 调节 PD 相关炎症和多巴胺能神经元损失的机制尚未完全阐明。在本研究中，我们旨在探讨lncRNA KCNQ1反向链/反义转录本1（KCNQ1OT1）在调节PD炎症小体激活中的功能和潜在机制。功能测定证实，KCNQ1OT1 的敲低可抑制 PD 模型小鼠中小胶质细胞 NLR 家族 Pyrin 结构域 3 (NLRP3) 炎性体激活并减轻多巴胺能神经元损失。由于KCNQ1OT1同时位于小胶质细胞的细胞质和细胞核中，我们证明KCNQ1OT1通过与细胞质中的miR-186竞争性结合促进小胶质细胞NLRP3炎症小体活化，并通过招募DiGeorge综合征关键区基因8（DGCR8）抑制pri-miR-186介导的NLRP3沉默。 ）分别在核中。我们的研究在小胶质细胞介导的 NLRP3 炎症小体激活和多巴胺能神经元损失中发现了一种新型的 lncRNA-pri-miRNA/mature miRNA-mRNA 调控网络，为帕金森病的治疗提供了进一步的见解。版权所有 © 2024。由 Elsevier B.V. 出版。

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.Copyright © 2024. Published by Elsevier B.V.