Coupling of the NMDA receptor to neuroprotective and neurodestructive events.
Coupling of the NMDA receptor to neuroprotective and neurodestructive events.
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DOI：
10.1042/bst0371147
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发表时间：
2009-12
影响因子：
3.9
通讯作者：
Hardingham GE
中科院分区：
文献类型：
--
作者：
Hardingham GE
NMDA受体是离子型谷氨酸受体的一个亚型，在中枢神经元的生理和病理生理中起重要作用。通过NMDA受体的不适当水平的Ca2+内流可导致急性创伤如局部缺血和创伤性脑损伤以及某些神经变性疾病如亨廷顿病中的神经元损失。然而，NMDA受体活性的正常生理模式可以促进对细胞凋亡和兴奋毒性损伤的神经保护。因此，NMDA受体阻滞剂可促进神经元完全死亡或使其易受继发性创伤。因此，对NMDA受体活性的反应遵循经典的激素剂量反应曲线：太多和太少都是有害的。人们对NMDA受体活性的神经保护和神经破坏作用的分子机制以及决定NMDA受体活性的发生是有害还是有益的因素的了解越来越多。越来越明显的是，氧化应激在促进神经元死亡中起作用，这两者都响应于NMDA受体的高活性和低活性。在这一领域的了解增加导致兴奋性毒性疾病的新的治疗靶点和策略的发现，以及NMDA受体阻滞剂的有害后果的日益升值。
NMDA receptors are a subtype of ionotropic glutamate receptor with an important role in the physiology and pathophysiology of central neurons. Inappropriate levels of Ca2+ influx through the NMDA receptor can contribute to neuronal loss in acute trauma such as ischemia and traumatic brain injury, as well as certain neurodegenerative diseases such as Huntington’s. However, normal physiological patterns of NMDA receptor activity can promote neuroprotection against both apoptotic and excitotoxic insults. As a result, NMDA receptor blockade can promote neuronal death outright or render them vulnerable to secondary trauma. Thus, responses to NMDA receptor activity follow a classical hormetic dose-response curve: both too much and too little can be harmful. There is a growing knowledge of the molecular mechanisms underlying both the neuroprotective and neurodestructive effects of NMDA receptor activity, as well as the factors that determine whether an episode of NMDA receptor activity is harmful or beneficial. It is becoming apparent that oxidative stress plays a role in promoting neuronal death both in response to both hyper- and hypoactivity of the NMDA receptor. Increased understanding in this field is leading to the discovery of new therapeutic targets and strategies for excitotoxic disorders, as well as a growing appreciation of the harmful consequences of NMDA receptor blockade.