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- Title
A lincRNA-p21/miR-181 family feedback loop regulates microglial activation during systemic LPS- and MPTP- induced neuroinflammation.
- Authors
Ye, Yongyi; He, Xiaozheng; Lu, Fengfei; Mao, Hengxu; Zhu, Zhiyuan; Yao, Longping; Luo, Wanxian; Sun, Xiang; Wang, Baoyan; Qian, Chen; Zhang, Yizhou; Lu, Guohui; Zhang, Shizhong
- Abstract
The role of microglial-mediated sustained neuroinflammation in the onset and progression of Parkinson’s disease (PD) is well established, but the mechanisms contributing to microglial activation remain unclear. LincRNA-p21, a well studied long intergenic noncoding RNA (lincRNA), plays pivotal roles in diverse biological processes and diseases. Its role in microglial activation and inflammation-induced neurotoxicity, however, has not yet been fully elucidated. Here, we report that lincRNA-p21 promotes microglial activation through a p53-dependent transcriptional pathway. We further demonstrate that lincRNA-p21 competitively binds to the miR-181 family and induces microglial activation through the miR-181/PKC-δ pathway. Moreover, PKC-δ induction further increases the expression of p53/lincRNA-p21 and thus forms a circuit. Taken together, our results suggest that p53/lincRNA-p21, together with miR-181/PKC-δ, form a double-negative feedback loop that facilitates sustained microglial activation and the deterioration of neurodegeneration.
- Publication
Cell Death & Disease, 2018, Vol 9, Issue 8, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-018-0821-5