Mattson M P, Culmsee C, Yu Z, Camandola S
Sanders-Brown Research Center on Aging and Department of Anatomy and Neurobiology, University of Kentucky, Lexington, USA.
J Neurochem. 2000 Feb;74(2):443-56. doi: 10.1046/j.1471-4159.2000.740443.x.
The transcription factor nuclear factor kappaB (NF-kappaB) is moving to the forefront of the fields of apoptosis and neuronal plasticity because of recent findings showing that activation of NF-kappaB prevents neuronal apoptosis in various cell culture and in vivo models and because NF-kappaB is activated in association with synaptic plasticity. Activation of NF-kappaB was first shown to mediate antiapoptotic actions of tumor necrosis factor in cultured neurons and was subsequently shown to prevent death of various nonneuronal cells. NF-kappaB is activated by several cytokines and neurotrophic factors and in response to various cell stressors. Oxidative stress and elevation of intracellular calcium levels are particularly important inducers of NF-kappaB activation. Activation of NF-kappaB can interrupt apoptotic biochemical cascades at relatively early steps, before mitochondrial dysfunction and oxyradical production. Gene targets for NF-kappaB that may mediate its antiapoptotic actions include the antioxidant enzyme manganese superoxide dismutase, members of the inhibitor of apoptosis family of proteins, and the calcium-binding protein calbindin D28k. NF-kappaB is activated by synaptic activity and may play important roles in the process of learning and memory. The available data identify NF-kappaB as an important regulator of evolutionarily conserved biochemical and molecular cascades designed to prevent cell death and promote neuronal plasticity. Because NF-kappaB may play roles in a range of neurological disorders that involve neuronal degeneration and/or perturbed synaptic function, pharmacological and genetic manipulations of NF-kappaB signaling are being developed that may prove valuable in treating disorders ranging from Alzheimer's disease to schizophrenia.
转录因子核因子κB（NF-κB）正迈向细胞凋亡和神经元可塑性领域的前沿，这是因为最近的研究发现表明，NF-κB的激活在各种细胞培养和体内模型中可防止神经元凋亡，还因为NF-κB的激活与突触可塑性相关。NF-κB的激活最初被证明可介导肿瘤坏死因子在培养神经元中的抗凋亡作用，随后又被证明可防止各种非神经元细胞的死亡。NF-κB可被多种细胞因子和神经营养因子激活，并对各种细胞应激源作出反应。氧化应激和细胞内钙水平升高是NF-κB激活的特别重要的诱导因素。在出现线粒体功能障碍和氧自由基产生之前，NF-κB的激活可在相对早期阶段中断凋亡生化级联反应。可能介导其抗凋亡作用的NF-κB的基因靶点包括抗氧化酶锰超氧化物歧化酶、凋亡抑制蛋白家族成员以及钙结合蛋白钙结合蛋白D28k。NF-κB可被突触活动激活，并可能在学习和记忆过程中发挥重要作用。现有数据表明NF-κB是进化上保守的生化和分子级联反应的重要调节因子，这些级联反应旨在防止细胞死亡并促进神经元可塑性。由于NF-κB可能在一系列涉及神经元变性和/或突触功能紊乱的神经疾病中起作用，因此正在开发对NF-κB信号进行药理学和遗传学操作的方法，这些方法可能在治疗从阿尔茨海默病到精神分裂症等疾病方面具有重要价值。
