Department of Pharmacology and Laboratory of Aging and Nervous Diseases (SZS0703), Soochow University School of Medicine, WenJing Road, 215123 Suzhou, China.
Apoptosis. 2010 Nov;15(11):1382-402. doi: 10.1007/s10495-010-0481-0.
Glutamate receptor-mediated excitatory neurotransmission plays a key role in neural development, differentiation and synaptic plasticity. However, excessive stimulation of glutamate receptors induces neurotoxicity, a process that has been defined as excitotoxicity. Excitotoxicity is considered to be a major mechanism of cell death in a number of central nervous system diseases including stroke, brain trauma, epilepsy and chronic neurodegenerative disorders. Unfortunately clinical trials with glutamate receptor antagonists, that would logically prevent the effects of excessive receptor activation, have been associated with untoward side effects or little clinical benefit. Therefore, uncovering molecular pathways involved in excitotoxic neuronal death is of critical importance to future development of clinical treatment of many neurodegenerative disorders where excitotoxicity has been implicated. This review discusses the current understanding of the molecular and cellular mechanisms of excitotoxicity and their roles in the pathogenesis of diseases of the central nervous system.
谷氨酸受体介导的兴奋性神经递质传递在神经发育、分化和突触可塑性中发挥着关键作用。然而，谷氨酸受体的过度刺激会导致神经毒性，这一过程被定义为兴奋性毒性。兴奋性毒性被认为是中风、脑创伤、癫痫和慢性神经退行性疾病等多种中枢神经系统疾病中细胞死亡的主要机制。不幸的是，用谷氨酸受体拮抗剂进行的临床试验，从逻辑上讲可以防止过度受体激活的影响，但与不良副作用或很少有临床益处相关。因此，揭示兴奋性神经元死亡中涉及的分子途径对于未来许多神经退行性疾病的临床治疗的发展至关重要，因为兴奋性毒性已被牵连其中。这篇综述讨论了目前对兴奋性毒性的分子和细胞机制的理解及其在中枢神经系统疾病发病机制中的作用。
