Microglia Purinoceptor P2Y6: An Emerging Therapeutic Target in CNS Diseases

被引:38
作者
Anwar, Shehata [1 ,2 ]
Pons, Vincent [1 ]
Rivest, Serge [1 ]
机构
[1] Laval Univ, Fac Med, CHU Quebec Res Ctr CHUL, Dept Mol Med,Neurosci Lab, Quebec City, PQ G1V 0A6, Canada
[2] Beni Suef Univ, Fac Vet Med, Dept Pathol, Bani Suwayf 62511, Egypt
关键词
microglia; phagocytosis; neuroinflammation; pro-inflammatory cytokines; MOLECULAR-MECHANISMS; NUCLEOTIDE RECEPTORS; AUTOPHAGY; PHAGOCYTOSIS; UDP; INFLAMMATION; INHIBITION; ACTIVATION; CELLS; NEUROINFLAMMATION;
D O I
10.3390/cells9071595
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The purinergic receptor P2Y6 is expressed in immune cells, including the microglia that are implicated in neurological disorders. Its ligand, UDP, is a signaling molecule that can serve as an "find-me" signal when released in significant quantities by damaged/dying cells. The binding of UDP by P2Y6R leads to the activation of different biochemical pathways, depending on the disease context and the pathological environment. Generally, P2Y6R stimulates phagocytosis. However, whether or not phagocytosis coincides with cell activation or the secretion of pro-inflammatory cytokines needs further investigation. The current review aims to discuss the various functions of P2Y6R in some CNS disorders. We present evidence that P2Y6R may have a detrimental or beneficial role in the nervous system, in the context of neurological pathologies, such as ischemic stroke, Alzheimer's disease, Parkinson's disease, radiation-induced brain injury, and neuropathic pain.
引用
收藏
页数:13
相关论文
共 101 条
[1]   International union of pharmacology LVIII: Update on the P2Y G protein-coupled nucleotide receptors: From molecular mechanisms and pathophysiology to therapy [J].
Abbracchio, Maria P. ;
Burnstock, Geoffrey ;
Boeynaems, Jean-Marie ;
Barnard, Eric A. ;
Boyer, Jose L. ;
Kennedy, Charles ;
Knight, Gillian E. ;
Fumagalli, Marta ;
Gachet, Christian ;
Jacobson, Kenneth A. ;
Weisman, Gary A. .
PHARMACOLOGICAL REVIEWS, 2006, 58 (03) :281-341
[2]   P2Y2 and P2Y6 receptor activation elicits intracellular calcium responses in human adipose-derived mesenchymal stromal cells [J].
Ali, Seema ;
Turner, Jeremy ;
Fountain, Samuel J. .
PURINERGIC SIGNALLING, 2018, 14 (04) :371-384
[3]   How Intensive Should Radiotherapy for Head and Neck Cancer With Synchronous Distant Metastases Be? Review of Cases [J].
Ampil, Federico L. ;
Kim, David D. ;
Ghali, Ghali E. ;
Baluna, Roxana G. .
JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, 2012, 70 (03) :730-733
[4]   Alzheimer's disease: microglia targets and their modulation to promote amyloid phagocytosis and mitigate neuroinflammation [J].
Anwar, Shehata ;
Rivest, Serge .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2020, 24 (04) :331-344
[5]   Inhibition of P2X4 Function by P2Y6 UDP Receptors in Microglia [J].
Bernier, Louis-Philippe ;
Ase, Ariel R. ;
Boue-Grabot, Eric ;
Seguela, Philippe .
GLIA, 2013, 61 (12) :2038-2049
[6]   P2Y6 Receptor-Mediated Spinal Microglial Activation in Neuropathic Pain [J].
Bian, Jiang ;
Zhang, Ying ;
Liu, Yan ;
Li, Qun ;
Tang, Hai-bin ;
Liu, Qing .
PAIN RESEARCH & MANAGEMENT, 2019, 2019
[7]   Discovery of purinergic signalling, the initial resistance and current explosion of interest [J].
Burnstock, G. .
BRITISH JOURNAL OF PHARMACOLOGY, 2012, 167 (02) :238-255
[8]   IS THERE A BASIS FOR DISTINGUISHING 2 TYPES OF P2-PURINOCEPTOR [J].
BURNSTOCK, G ;
KENNEDY, C .
GENERAL PHARMACOLOGY, 1985, 16 (05) :433-440
[9]  
BURNSTOCK G, 1972, PHARMACOL REV, V24, P509
[10]   Cellular distribution and functions of P2 receptor subtypes in different systems [J].
Burnstock, G ;
Knight, GE .
INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL. 240, 2004, 240 :31-+