| First Author | Zhou Y | Year | 2016 |
| Journal | Mol Neurodegener | Volume | 11 |
| Pages | 28 | PubMed ID | 27084336 |
| Mgi Jnum | J:264999 | Mgi Id | MGI:6198992 |
| Doi | 10.1186/s13024-016-0094-3 | Citation | Zhou Y, et al. (2016) MicroRNA-7 targets Nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson's disease. Mol Neurodegener 11:28 |
| abstractText | BACKGROUND: alpha-Synuclein (alpha-Syn), a pathological hallmark of Parkinson's disease (PD), has been recognized to induce the production of interleukin-1beta in a process that depends, at least in vitro, on nod-like receptor protein 3 (NLRP3) inflammasome in monocytes. However, the role of NLRP3 inflammasome activation in the onset of PD has not yet been fully established. RESULTS: In this study, we showed that NLRP3 inflammasomes were activated in the serum of PD patients and the midbrain of PD model mice. We further clarified that alpha-syn activated the NLRP3 inflammasome through microglial endocytosis and subsequent lysosomal cathepsin B release. Deficiency of caspase-1, an important component of NLRP3 inflammasome, significantly inhibited alpha-syn-induced microglia activation and interleukin-1beta production, which in turn alleviated the reduction of mesencephalic dopaminergic neurons treated by microglia medium. Specifically, we demonstrated for the first time that Nlrp3 is a target gene of microRNA-7 (miR-7). Transfection of miR-7 inhibited microglial NLRP3 inflammasome activation whereas anti-miR-7 aggravated inflammasome activation in vitro. Notably, stereotactical injection of miR-7 mimics into mouse striatum attenuated dopaminergic neuron degeneration accompanied by the amelioration of microglial activation in MPTP-induced PD model mice. CONCLUSIONS: Our study provides a direct link between miR-7 and NLRP3 inflammasome-mediated neuroinflammation in the pathogenesis of PD. These findings will give us an insight into the potential of miR-7 and NLRP3 inflammasome in terms of opening up novel therapeutic avenues for PD. |
