P2X7 Receptor Signaling Pathway as a Therapeutic Target for Neurodegenerative Diseases
P2X7 Receptor Signaling Pathway as a Therapeutic Target for Neurodegenerative Diseases
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DOI：
10.1007/s00005-010-0069-y
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发表时间：
2010-02
影响因子：
3.2
通讯作者：
T. Takenouchi;K. Sekiyama;A. Sekigawa;M. Fujita;M. Waragai;S. Sugama;Y. Iwamaru;H. Kitani;M. Hashim
中科院分区：
文献类型：
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作者：
T. Takenouchi;K. Sekiyama;A. Sekigawa;M. Fujita;M. Waragai;S. Sugama;Y. Iwamaru;H. Kitani;M. Hashim
最近的一项研究表明，神经炎症在许多神经退行性疾病（例如阿尔茨海默病和帕金森病）的发病机制中发挥着重要作用。尽管确切的机制尚不清楚，但小胶质细胞信号转导途径的失调可能会增强炎症，导致突触功能障碍并最终导致神经元细胞死亡。 P2X7 受体 (P2X7R) 是一种在大脑小胶质细胞中大量表达的 ATP 门控离子通道，其表达和功能在阿尔茨海默病患者和各种神经退行性疾病动物模型的死后大脑中显着上调。这支持了 P2X7R 通路在神经变性进展中的作用。使用亮蓝 G（一种可以穿过血脑屏障的 P2X7R 拮抗剂）阻断 P2X7R 已被证明可以改善各种动物模型的神经病理学。总而言之，这些结果提出了 P2X7R 信号通路可能成为治疗各种神经退行性疾病的治疗靶点的可能性。
A recent study suggested that neuroinflammation plays a major role in the pathogenesis of a number of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Although the precise mechanism is obscure, dysregulation of the signaling transduction pathway in microglia may enhance inflammation, leading to synaptic dysfunction and ultimately to neuronal cell death. The expression and function of the P2X7 receptor (P2X7R), an ATP-gated ion channel abundantly expressed in microglia in the brain, is significantly up-regulated in the postmortem brain of Alzheimer’s disease patients and various neurodegenerative disease animal models. This supports the role of the P2X7R pathway in the progression of neurodegeneration. Blocking P2X7R using brilliant blue G, a P2X7R antagonist that can cross the blood–brain barrier, has been shown to result in the amelioration of neuropathology in various animal models. Taken together, these results raise the possibility that the P2X7R signaling pathway could be a therapeutic target for treating various neurodegenerative diseases.