Microglia is believed to exacerbate the loss of dopaminergic neurons within the SN once they are persistently activated 4, 5. In recent years, neuroinflammation, essentially mediated by chronic and sustained activated microglia, has been receiving particular attention 1, 2, 3.
The underlying molecular mechanisms of PD are still poorly understood. Parkinson’s disease (PD) is the second most common neurodegenerative disorder, with evolving layers of complexity. 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. Moreover, PKC-δ induction further increases the expression of p53/lincRNA-p21 and thus forms a circuit. We further demonstrate that lincRNA-p21 competitively binds to the miR-181 family and induces microglial activation through the miR-181/PKC-δ pathway. Here, we report that lincRNA-p21 promotes microglial activation through a p53-dependent transcriptional pathway.
Its role in microglial activation and inflammation-induced neurotoxicity, however, has not yet been fully elucidated. LincRNA-p21, a well studied long intergenic noncoding RNA (lincRNA), plays pivotal roles in diverse biological processes and diseases. 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.