The microglial P2Y6 receptor as a therapeutic target for neurodegenerative diseases

被引：2
|
作者：
Dundee, Jacob M. [1 ]
Brown, Guy C. [1 ]
机构：
[1] Univ Cambridge, Dept Biochem, Cambridge, England
来源：
TRANSLATIONAL NEURODEGENERATION | 2024年 / 13卷 / 01期
基金：
英国医学研究理事会;
关键词：
Alzheimer's disease; Parkinson's disease; Neurodegeneration; Neuroinflammation; P2Y(6) receptor; Drug development; Microglia; NEURONAL DEATH; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; PROTEIN-KINASE; BINDING SITES; AMYLOID-BETA; PHAGOCYTOSIS; ACTIVATION; MODEL; INHIBITION;
D O I：
10.1186/s40035-024-00438-5
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Neurodegenerative diseases are associated with chronic neuroinflammation in the brain, which can result in microglial phagocytosis of live synapses and neurons that may contribute to cognitive deficits and neuronal loss. The microglial P2Y(6) receptor (P2Y(6)R) is a G-protein coupled receptor, which stimulates microglial phagocytosis when activated by extracellular uridine diphosphate, released by stressed neurons. Knockout or inhibition of P2Y(6)R can prevent neuronal loss in mouse models of Alzheimer's disease (AD), Parkinson's disease, epilepsy, neuroinflammation and aging, and prevent cognitive deficits in models of AD, epilepsy and aging. This review summarises the known roles of P2Y(6)R in the physiology and pathology of the brain, and its potential as a therapeutic target to prevent neurodegeneration and other brain pathologies.
引用
收藏
页数：11
相关论文
共 50 条
  • [31] The P2Y6 Receptor as a Potential Keystone in Essential Hypertension
    Daghbouche-Rubio, Nuria
    Alvarez-Miguel, Ines
    Flores, Victor Alejandro
    Rojo-Mencia, Jorge
    Navedo, Manuel
    Nieves-Citron, Madeleine
    Cidad, Pilar
    Perez-Garcia, M. Teresa
    Lopez-Lopez, Jose R.
    FUNCTION, 2024, 5 (06):
  • [32] The P2Y6 Receptor Stimulates Bone Resorption by Osteoclasts
    Orriss, Isabel R.
    Wang, Ning
    Burnstock, Geoffrey
    Arnett, Timothy R.
    Gartland, Alison
    Robaye, Bernard
    Boeynaems, Jean-Marie
    ENDOCRINOLOGY, 2011, 152 (10) : 3706 - 3716
  • [33] Lack of specificity shown by P2Y6 receptor antibodies
    Yu, Weiqun
    Hill, Warren G.
    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2013, 386 (10) : 885 - 891
  • [34] Modification of Neural Circuit Functions by Microglial P2Y6 Receptors in Health and Neurodegeneration
    Zhang, Yi
    Tang, Yong
    Illes, Peter
    MOLECULAR NEUROBIOLOGY, 2025, 62 (04) : 4139 - 4148
  • [35] P2Y6 Receptor-Dependent Microglial Phagocytosis of Synapses during Development Regulates Synapse Density and Memory
    Dundee, Jacob M.
    Puigdellivol, Mar
    Butler, Richard
    Brown, Guy C.
    JOURNAL OF NEUROSCIENCE, 2023, 43 (48): : 8090 - 8103
  • [36] P2Y6 receptor and immunoinflammationP2Y6受体与免疫炎症
    Gui-Dong Liu
    Jian-Qing Ding
    Qin Xiao
    Sheng-Di Chen
    Neuroscience Bulletin, 2009, 25 : 161 - 164
  • [37] Knockout of purinergic receptor Y6 (P2Y6) leads to cardiomyopathy in mice
    Ahmed, I.
    Merz, J.
    Rofa, K.
    Dufner, B.
    Schickmeier, J.
    Hoppe, N.
    Hilgendorf, I.
    Bode, C.
    Zirlik, A.
    Stachon, P.
    EUROPEAN HEART JOURNAL, 2018, 39 : 593 - 593
  • [38] FUNCTIONAL MODULATION OF MICROGLIAL P2X4 RECEPTOR-CHANNELS BY UDP-ACTIVATED P2Y6 RECEPTORS
    Bernier, L. P.
    Ase, A. R.
    Boue-Grabot, E.
    Seguela, P.
    JOURNAL OF NEUROCHEMISTRY, 2011, 118 : 31 - 31
  • [39] Microglial P2Y6 6 calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis
    Umpierre, Anthony D.
    Li, Bohan
    Ayasoufi, Katayoun
    Simon, Whitney L.
    Zhao, Shunyi
    Xie, Manling
    Thyen, Grace
    Hur, Benjamin
    Zheng, Jiaying
    Liang, Yue
    Bosco, Dale B.
    Maynes, Mark A.
    Wu, Zhaofa
    Yu, Xinzhu
    Sung, Jaeyun
    Johnson, Aaron J.
    Li, Yulong
    Wu, Long-Jun
    NEURON, 2024, 112 (12) : 1959 - 1977.e10
  • [40] P2Y6 and vascular inflammation
    Blackburn, Michael R.
    BLOOD, 2011, 117 (08) : 2304 - 2305
12345