The microglial P2Y6 receptor as a therapeutic target for neurodegenerative diseases

被引：5
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.
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页数：11
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