Glutamate excitotoxicity is a central mechanism contributing to cellular dysfunction and death in various neurological disorders and diseases, such as stroke, traumatic brain injury, epilepsy, schizophrenia, addiction, mood disorders, Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, pathologic pain, and even normal aging-related changes. This detrimental effect emerges from glutamate binding to glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, N-methyl-d-aspartate receptors, kainate receptors, and GluD receptors. Thus, excitotoxicity could be prevented by targeting glutamate receptors and their downstream signaling pathways. However, almost all the glutamate receptor antagonists failed to attenuate excitotoxicity in human patients, mainly due to the limited understanding of the underlying mechanisms regulating excitotoxicity. Transient receptor potential (TRP) channels serve as ancient cellular sensors capable of detecting and responding to both external and internal stimuli. The study of human TRP channels has flourished in recent decades since the initial discovery of mammalian TRP in 1995. These channels have been found to play pivotal roles in numerous pathologic conditions, including excitotoxicity. In this review, our focus centers on exploring the intricate interactions between TRP channels and glutamate receptors in excitotoxicity.

中文翻译：

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兴奋性毒性中的 TRP 通道

谷氨酸兴奋性毒性是多种神经系统疾病和疾病中导致细胞功能障碍和死亡的核心机制，例如中风、创伤性脑损伤、癫痫、精神分裂症、成瘾、情绪障碍、亨廷顿病、阿尔茨海默病、帕金森病、多发性硬化症、病理性疼痛，甚至是与衰老相关的正常变化。这种有害作用源于谷氨酸与谷氨酸受体的结合，包括α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体、N-甲基-d-天冬氨酸受体、红藻氨酸受体和GluD受体。因此，可以通过靶向谷氨酸受体及其下游信号通路来预防兴奋性毒性。然而，几乎所有谷氨酸受体拮抗剂都未能减轻人类患者的兴奋性毒性，这主要是由于对调节兴奋性毒性的潜在机制了解有限。瞬时受体电位 (TRP) 通道作为古老的细胞传感器，能够检测和响应外部和内部刺激。自 1995 年首次发现哺乳动物 TRP 以来，近几十年来，人类 TRP 通道的研究蓬勃发展。人们发现这些通道在许多病理状况（包括兴奋性毒性）中发挥着关键作用。在这篇综述中，我们的重点是探索兴奋性毒性中 TRP 通道和谷氨酸受体之间复杂的相互作用。