Objective: To investigate whether the purinoceptor P2Y6 can be used as a biomarker in the diagnosis and treatment of Parkinson’s disease (PD) and the role in the neuroinflammation.

Background: Microglia are the major cellular elements with immune activity and play important roles in the pathogenesis of neurodegenerative diseases especially PD. Previous studies showed that purinoceptor P2Y6 mainly contributed to the microglial phagocytosis of dying neurons. Whether P2Y6 receptor takes part in the process of neuroinflammation and can be used as a biomarker in PD are largely unknown.

Methods: We clarified the difference of P2Y6 receptor expression level in the peripheral blood mononuclear cells among 145 PD patients, 170 healthy control and 30 Parkinson plus syndrome (PS) patients. We also explored the correlation between P2Y6 receptor expression level and basic clinical features of PD patients. We then used a BV2 cell culture model that could represent a state of brain inflammation. The cultures obtained were used to investigate i) the effect of LPS on P2Y6 expression ii) the effect of LPS on UDP expression used HPLC iii) the effect of UDP/P2Y6 signaling on cytokine expression iv) the signaling pathways activated by the P2Y6 receptor involved in the neuroinflammation.

Results: Expression of P2Y6 receptor in PD patients were higher than healthy control and PS patients, which had no relationship with disease severity or the differences of drug-using. The ROC curve between PD patients and healthy controls shows that the diagnostic cut-off point is 1.65 (sensitivity 82.1%, specificity 64.6%) for the diagnosis of PD; the ROC curve between PD patients and PS patients shows that the diagnostic cut-off point is 1.16 (sensitivity 91%, specificity 57.1%) for the differential diagnosis of PD. In the in vitro experiments, we found that the P2Y6 receptor was involved in proinflammatory factors release stimulated by LPS, through an autocrine loop based on LPS-triggered UDP secretion, leading to death of dopaminergic neurons partially dependent on ERK1/2 pathway. Importantly, we also found that knock down or blocking P2Y6 receptor could reverse these pathological processes.

Conclusions: P2Y6 receptor can be a potential biomarker of PD and it is involved in the neuroinflammation. Blocking P2Y6 receptor can be a potential therapeutic approach for the treatment of patients with PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/microglia-p2y6-receptor-is-related-to-parkinsons-disease-and-involved-in-the-neuroinflammatory-process/