{"title":"作为神经退行性疾病治疗靶点的小胶质细胞 P2Y6 受体。","authors":"Jacob M Dundee, Guy C Brown","doi":"10.1186/s40035-024-00438-5","DOIUrl":null,"url":null,"abstract":"<p><p>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<sub>6</sub> receptor (P2Y<sub>6</sub>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<sub>6</sub>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<sub>6</sub>R in the physiology and pathology of the brain, and its potential as a therapeutic target to prevent neurodegeneration and other brain pathologies.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"47"},"PeriodicalIF":10.8000,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380353/pdf/","citationCount":"0","resultStr":"{\"title\":\"The microglial P2Y<sub>6</sub> receptor as a therapeutic target for neurodegenerative diseases.\",\"authors\":\"Jacob M Dundee, Guy C Brown\",\"doi\":\"10.1186/s40035-024-00438-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sub>6</sub> receptor (P2Y<sub>6</sub>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<sub>6</sub>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<sub>6</sub>R in the physiology and pathology of the brain, and its potential as a therapeutic target to prevent neurodegeneration and other brain pathologies.</p>\",\"PeriodicalId\":23269,\"journal\":{\"name\":\"Translational Neurodegeneration\",\"volume\":\"13 1\",\"pages\":\"47\"},\"PeriodicalIF\":10.8000,\"publicationDate\":\"2024-09-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380353/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational Neurodegeneration\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s40035-024-00438-5\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Neurodegeneration","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40035-024-00438-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
神经退行性疾病与大脑中的慢性神经炎症有关，这种炎症可导致小胶质细胞吞噬活的突触和神经元，从而造成认知障碍和神经元丢失。小胶质细胞 P2Y6 受体（P2Y6R）是一种 G 蛋白偶联受体，当被受压神经元释放的细胞外二磷酸尿苷激活时，会刺激小胶质细胞的吞噬作用。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，敲除或抑制 P2Y6R 可防止神经元丢失，并在阿尔茨海默病、癫痫和衰老模型中防止认知缺陷。本综述总结了 P2Y6R 在大脑生理和病理中的已知作用，以及它作为治疗靶点预防神经变性和其他大脑病变的潜力。
The microglial P2Y6 receptor as a therapeutic target for neurodegenerative diseases.
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 P2Y6 receptor (P2Y6R) is a G-protein coupled receptor, which stimulates microglial phagocytosis when activated by extracellular uridine diphosphate, released by stressed neurons. Knockout or inhibition of P2Y6R 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 P2Y6R in the physiology and pathology of the brain, and its potential as a therapeutic target to prevent neurodegeneration and other brain pathologies.
期刊介绍：
Translational Neurodegeneration, an open-access, peer-reviewed journal, addresses all aspects of neurodegenerative diseases. It serves as a prominent platform for research, therapeutics, and education, fostering discussions and insights across basic, translational, and clinical research domains. Covering Parkinson's disease, Alzheimer's disease, and other neurodegenerative conditions, it welcomes contributions on epidemiology, pathogenesis, diagnosis, prevention, drug development, rehabilitation, and drug delivery. Scientists, clinicians, and physician-scientists are encouraged to share their work in this specialized journal tailored to their fields.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
