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Updated: Feb 7, 2026
Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model
Published on: January 7, 2019
A lincRNA-p21/miR-181 family feedback loop regulates microglial activation during systemic LPS- and MPTP- induced
Yongyi Ye1, Xiaozheng He1, Fengfei Lu1
1The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, China.
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.
Insights
Long intergenic noncoding RNA p21 (lincRNA-p21) drives Parkinson's disease neuroinflammation by activating microglia. This involves a p53-dependent pathway and a feedback loop with miR-181 and PKC-δ, worsening neurodegeneration.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Microglial-mediated neuroinflammation is crucial in Parkinson's disease (PD) pathogenesis.
- The precise mechanisms driving microglial activation in PD remain incompletely understood.
- Long intergenic noncoding RNAs (lincRNAs) influence various biological processes, but their role in PD neuroinflammation is largely unexplored.
Purpose of the Study:
- To investigate the role of lincRNA-p21 in microglial activation and neuroinflammation in Parkinson's disease.
- To elucidate the molecular pathways through which lincRNA-p21 modulates microglial function.
Main Methods:
- Investigated lincRNA-p21 expression and function in microglial activation models.
- Utilized p53-dependent transcriptional pathway analysis.
- Examined the interaction between lincRNA-p21 and the miR-181 family.
- Assessed the role of the miR-181/PKC-δ pathway in microglial activation.
- Analyzed the feedback circuit involving p53/lincRNA-p21 and miR-181/PKC-δ.
Main Results:
- lincRNA-p21 significantly promotes microglial activation via a p53-dependent transcriptional mechanism.
- lincRNA-p21 directly binds to and inhibits the miR-181 family.
- This interaction leads to microglial activation through the miR-181/PKC-δ pathway.
- A positive feedback loop is established where PKC-δ further upregulates p53 and lincRNA-p21.
Conclusions:
- The p53/lincRNA-p21 axis and the miR-181/PKC-δ pathway form a double-negative feedback loop.
- This regulatory circuit sustains microglial activation, contributing to neuroinflammation and neurodegeneration in Parkinson's disease.
- lincRNA-p21 represents a potential therapeutic target for modulating neuroinflammation in PD.
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