Marini A M, Jiang X, Wu X, Pan H, Guo Z, Mattson M P, Blondeau N, Novelli A, Lipsky R H
Department of Neurology and Neuroscience Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Amino Acids. 2007;32(3):299-304. doi: 10.1007/s00726-006-0414-y. Epub 2006 Sep 29.
The amino acid glutamate, the major excitatory neurotransmitter in the central nervous system, activates receptors coupled to calcium influx. Excessive activation of glutamate receptors in conditions such as severe epileptic seizures or stroke can kill neurons in a process called excitotoxicity. However, subtoxic levels of activation of the N-methyl-D-aspartate (NMDA) type of glutamate receptor elicit adaptive responses in neurons that enhance their ability to withstand more severe stress. A variety of stimuli induce adaptive responses to protect neurons. For example, sublethal ischemic episodes or a mild epileptic insult can protect neurons in a process referred to as tolerance. The molecular mechanisms that protect neurons by these different stressful stimuli are largely unknown but they share common features such as the transcription factor, nuclear factor kappa B (NF-kappaB), which is activated by ischemic and epileptic preconditioning as well as exposure to subtoxic NMDA concentrations. In this article, we describe stress-induced neuroprotective mechanisms highlighting the role of brain-derived neurotrophic factor (BDNF), a protein that plays a crucial role in neuronal survival and maintenance, neurogenesis and learning and memory.
氨基酸谷氨酸是中枢神经系统中主要的兴奋性神经递质，它可激活与钙内流相关的受体。在严重癫痫发作或中风等情况下，谷氨酸受体的过度激活会在一个称为兴奋毒性的过程中杀死神经元。然而，N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体的亚毒性激活水平会在神经元中引发适应性反应，从而增强它们承受更严重应激的能力。多种刺激可诱导适应性反应以保护神经元。例如，亚致死性缺血发作或轻度癫痫损伤可在一个称为耐受的过程中保护神经元。这些不同应激刺激保护神经元的分子机制在很大程度上尚不清楚，但它们具有共同特征，如转录因子核因子κB（NF-κB），它可被缺血和癫痫预处理以及暴露于亚毒性NMDA浓度激活。在本文中，我们描述了应激诱导的神经保护机制，重点介绍了脑源性神经营养因子（BDNF）的作用，BDNF是一种在神经元存活与维持、神经发生以及学习和记忆中起关键作用的蛋白质。
