title: Microglia P2Y6 receptor is related to Parkinson's disease through neuroinflammatory process.
abstract: Microglia in the central nervous system (CNS) were reported to play crucial role in neurodegeneration. Previous studies showed that P2Y6 receptor (P2Y6R) mainly contributed to microglia activation and phagocytosis in CNS. However, the level of P2Y6R in Parkinson's disease (PD) patients is unclear. Therefore, we measured the level of P2Y6R in PD patients and speculated whether it could be a potential biomarker for PD. Given on the basis that P2Y6R was higher in PD patients, we further explored the mechanisms underlying P2Y6R in the pathogenesis of PD.
  
  
  
  We tested the expression level of P2Y6R in the peripheral blood mononuclear cells (PBMCs) among 145 PD patients, 170 healthy controls, and 30 multiple system atrophy (MSA) patients. We also used a lipopolysaccharide (LPS)-stimulated microglial cell culture model to investigate (i) the effects of LPS on P2Y6R expression with western blot and RT-PCR, (ii) the effects of LPS on UDP expression using HPLC, (iii) the effects of UDP/P2Y6R signaling on cytokine expression using western blot, RT-PCR, and ELISA, and (iv) the signaling pathways activated by the P2Y6R involved in the neuroinflammation.
  
  
  
  Expression levels of P2Y6R in PD patients were higher than healthy controls and MSA patients. P2Y6R could be a good biomarker of PD. P2Y6R was also upregulated in LPS-treated BV-2 cells and involved in proinflammatory cytokine release through an autocrine loop based on LPS-triggered UDP secretion and accelerated neuroinflammatory responses through the ERK1/2 pathway. Importantly, blocking UDP/P2Y6R signaling could reverse these pathological processes.
  
  
  
  P2Y6R may be a potential clinical biomarker of PD. Blocking P2Y6R may be a potential therapeutic approach to the treatment of PD patients through inhibition of microglia-activated neuroinflammation.
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lou
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
authors.forename: Guidong
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China. jqding18@yahoo.com.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China. louyue@163.com.
authors.forename: Shengdi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China. xiaoqin67@medmail.com.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Xiao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis*
chemical_list: D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6
keywords: Microglia; Neuroinflammation; P2Y6 receptor; Parkinson’s disease