Greene J G, Greenamyre J T
Department of Neurobiology and Anatomy, University of Rochester Medical Center, NY 14642, USA.
Prog Neurobiol. 1996 Apr;48(6):613-34. doi: 10.1016/0301-0082(96)00006-8.
Bioenergetic defects and abnormalities in glutamate neurotransmission have both been proposed to play important roles in neurological diseases of varying chronology, etiology and pathology. Recent experimental evidence suggests an intimate relationship between these two systems. Metabolic inhibition predisposes neurons to glutamate-mediated "excitotoxic" damage. The exact mechanism of this increased susceptibility is yet to be defined, but may involve, singly or in combination, decreased voltage-dependent Mg2+ blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, abnormalities in cellular Ca2+ homeostasis, or elevated production of reactive oxygen species. It is believed that enhancement of excitotoxicity by impaired metabolism may be a ubiquitous mechanism of neuronal death in neurological disease. Further elucidation of the exact mechanism of this enhancement may lead to the discovery of new targets for therapeutic intervention.
生物能量缺陷和谷氨酸神经传递异常均被认为在不同病程、病因和病理的神经疾病中起重要作用。最近的实验证据表明这两个系统之间存在密切关系。代谢抑制使神经元易受谷氨酸介导的“兴奋性毒性”损伤。这种易感性增加的确切机制尚待确定，但可能单独或联合涉及谷氨酸受体N-甲基-D-天冬氨酸（NMDA）亚型的电压依赖性Mg2+阻断减少、细胞Ca2+稳态异常或活性氧产生增加。据信，代谢受损导致的兴奋性毒性增强可能是神经疾病中神经元死亡的普遍机制。进一步阐明这种增强的确切机制可能会发现新的治疗干预靶点。
