Transcription factor NF-kappa B is activated in primary neurons by amyloid beta peptides and in neurons surrounding early plaques from patients with Alzheimer disease
Transcription factor NF-kappa B is activated in primary neurons by amyloid beta peptides and in neurons surrounding early plaques from patients with Alzheimer disease
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DOI：
10.1073/pnas.94.6.2642
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发表时间：
1997-03-18
影响因子：
11.1
通讯作者：
Kaltschmidt, C
中科院分区：
文献类型：
--
作者：
Kaltschmidt, B;Uherek, M;Kaltschmidt, C
含淀粉样β肽（A β）的斑块神经毒性A β是斑块的主要成分，是原代神经元中转录因子NF-κ B的有效激活剂，这种激活需要活性氧中间体作为信使，因为抗氧化剂阻止A β诱导的NF-κ B激活，用0.1 μ M A β-（1-40）和0.1 μ M A β-（25-35）片段发现NF-κ B的最大活化，使得NF-κ B在神经保护中的作用可行。使用p65 NF-κ B亚基的活性特异性mAb，在阿尔茨海默病患者脑切片的神经元和星形胶质细胞中也观察到NF-β B的活化。活化的NF-κ B局限于早期斑块附近的细胞。我们的数据表明，患病神经组织中的异常基因表达至少部分是由于A β诱导的NF-κ B激活，NF-κ B是许多促炎基因的一种有效的立即早期转录调节因子。
Amyloid beta peptide (A beta)-containing plaques neurotoxic A beta, a major plaque component, is a potent activator of the transcription factor NF-kappa B in primary neurons, This activation required reactive oxygen intermediates as messengers because an antioxidant prevented A beta-induced NF-kappa B activation, Maximal activation of NF-kappa B was found with 0.1 mu M A beta-(1-40) and 0.1 mu M A beta-(25-35) fragments, making a role for NF-kappa B in neuroprotection feasible, Using an activity-specific mAb for the p65 NF-kappa B subunit, activation of NF-beta B also was observed in neurons and astroglia of brain sections from Alzheimer disease patients, Activated NF-kappa B was restricted to cells in the close vicinity of early plaques. Our data suggest that the aberrant gene expression in diseased nervous tissue is at least in part due to A beta-induced activation of NF-kappa B, a potent immediate-early transcriptional regulator of numerous proinflammatory genes.