Division of Applied and Interventional Research, Toronto Western Research Institute, 399 Bathurst Street, Toronto, ON, Canada, M5T 2S8.
Pflugers Arch. 2010 Jul;460(2):525-42. doi: 10.1007/s00424-010-0809-1. Epub 2010 Mar 14.
Glutamate excitotoxicity is a hypothesis that states excessive glutamate causes neuronal dysfunction and degeneration. As glutamate is a major excitatory neurotransmitter in the central nervous system (CNS), the implications of glutamate excitotoxicity are many and far-reaching. Acute CNS insults such as ischaemia and traumatic brain injury have traditionally been the focus of excitotoxicity research. However, glutamate excitotoxicity has also been linked to chronic neurodegenerative disorders such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease and others. Despite the continued research into the mechanisms of excitotoxicity, there are currently no pharmacological interventions capable of providing significant neuroprotection in the clinical setting of brain ischaemia or injury. This review addresses the current state of excitotoxic research, focusing on the structure and physiology of glutamate receptors; molecular mechanisms underlying excitotoxic cell death pathways and their interactions with each other; the evidence for glutamate excitotoxicity in acute neurologic diseases; laboratory and clinical attempts at modulating excitotoxicity; and emerging targets for excitotoxicity research.
谷氨酸兴奋性毒性是一种假说，即过量的谷氨酸会导致神经元功能障碍和退化。由于谷氨酸是中枢神经系统（CNS）中的主要兴奋性神经递质，谷氨酸兴奋性毒性的影响是多方面的，而且影响深远。急性中枢神经系统损伤，如缺血和创伤性脑损伤，一直是兴奋性毒性研究的重点。然而，谷氨酸兴奋性毒性也与肌萎缩侧索硬化症、多发性硬化症、帕金森病等慢性神经退行性疾病有关。尽管人们一直在研究兴奋性毒性的机制，但目前尚无能够在脑缺血或损伤的临床环境中提供显著神经保护作用的药理学干预措施。本综述讨论了兴奋性毒性研究的现状，重点介绍了谷氨酸受体的结构和生理学；兴奋性细胞死亡途径的分子机制及其相互作用；急性神经疾病中谷氨酸兴奋性毒性的证据；调节兴奋性毒性的实验室和临床尝试；以及兴奋性毒性研究的新兴靶点。
