Department of Biochemistry, University of Cambridge, Cambridge, UK.
Transl Neurodegener. 2024 Sep 7;13(1):47. doi: 10.1186/s40035-024-00438-5.
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 receptor (P2YR) is a G-protein coupled receptor, which stimulates microglial phagocytosis when activated by extracellular uridine diphosphate, released by stressed neurons. Knockout or inhibition of P2YR 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 P2YR in the physiology and pathology of the brain, and its potential as a therapeutic target to prevent neurodegeneration and other brain pathologies.
神经退行性疾病与大脑中的慢性神经炎症有关，这可能导致小胶质细胞吞噬活突触和神经元，从而导致认知缺陷和神经元丧失。小胶质细胞 P2Y 受体 (P2YR) 是一种 G 蛋白偶联受体，当被应激神经元释放的细胞外尿苷二磷酸激活时，会刺激小胶质细胞吞噬作用。在阿尔茨海默病 (AD)、帕金森病、癫痫、神经炎症和衰老的小鼠模型中，P2YR 的敲除或抑制可以防止神经元丧失，并防止 AD、癫痫和衰老模型中的认知缺陷。本综述总结了 P2YR 在大脑生理学和病理学中的已知作用及其作为预防神经退行性变和其他脑部病变的治疗靶点的潜力。
