P2X7 receptor/NLRP3 inflammasome complex and α-synuclein in peripheral blood mononuclear cells: a prospective study in neo-diagnosed, treatment-naïve Parkinson's disease.

Background Neuro, and likely systemic inflammation, with abnormal α-synuclein deposition, participate in the development of Parkinson's disease (PD). The P2X7 receptor/NLRP3 inflammasome complex is upregulated in the brain of PD patients. By a prospective approach, we explored the degree of systemic activation of such complex, and its regulatory mechanisms, in treatment-naive PD individuals. Methods Expression and functional activity of the inflammasome were measured in peripheral blood mononuclear cells of 25 newly diagnosed PD patients and 25 controls at baseline and after twelve months of pharmacologic treatment, exploring the involved intracellular signalling and its epigenetic regulation. Results De-novo PD patients were characterized by a systemic hyper-expression of the P2X7R/NLRP3 inflammasome platform, likely able to modulate lymphomonocyte α-synuclein, whose brain deposits represent the main pathogenetic factor of PD. A reduced JNK phosphorylation might be the intracellular signalling mediating this effect. miR-7 and miR-30, implied in the pathogenesis of PD and in the post-transcriptional control of α-synuclein and NLRP3 expression, were also increased in PD. After one year of usual anti-Parkinson treatments, such inflammatory platform was significantly reduced. Conclusions Mononuclear cells of newly diagnosed PD subjects display a hyper-expression of the P2X7R/NLRP3 inflammasome platform that seems to modulate cellular α-synuclein content and is reduced after PD treatment; an impaired JNK phosphorylation might be the intracellular signalling mediating this effect, undergoing an epigenetic regulation by miR-7 and miR-30.