The in vitro neuronal toxicity of pentraxins associated with Alzheimer's disease brain lesions
The in vitro neuronal toxicity of pentraxins associated with Alzheimer's disease brain lesions
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DOI：
10.1016/s0006-8993(98)00966-4
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发表时间：
1998-12-07
期刊：
影响因子：
2.9
通讯作者：
Johnson, RA
中科院分区：
文献类型：
--
作者：
Duong, TH;Acton, PJ;Johnson, RA
血清淀粉样蛋白P成分（AP）和c反应蛋白（CRP）是正常的血清成分，属于戊烷素蛋白家族。这些蛋白先前已通过免疫组织化学方法定位于阿尔茨海默病（AD）的脑病变。AP是淀粉样蛋白沉积物的恒定成分，包括在AD中发现的淀粉样蛋白沉积物。AP和CRP均局限于AD神经原纤维缠结。这些蛋白在阿尔茨海默病的病因学中有间接作用。我们研究了血清AP和CRP对人源性神经细胞系（hNT）的影响。在处理过的细胞培养中，在hNT神经元中检测到AP和CRP，表明细胞摄取了这些蛋白质。最低生理浓度（8 μ g/ml）的AP对hNT神经元有明显的毒性作用。CRP也显示出对hNT神经元的毒性，但在与炎症状态相容的水平（50 μ g/ml）。这些结果提示血清AP和CRP在AD的发病机制中有更直接的作用。(C) 1998 Elsevier Science B.V.版权所有
Serum amyloid P component (AP) and C-reactive protein (CRP) are normal serum components which belong to the pentraxin family of proteins. These proteins have been previously localized by immunohistochemical method to the brain lesions of Alzheimer's disease (AD). AP is a constant constituent of amyloid deposits including those found in AD. Both AP and CRP have been localized to AD neurofibrillary tangles. An indirect role for these proteins has been previously suggested in the etiology of AD. We studied the effects of serum AP and CRP on a human-derived neuronal cell line (hNT). In treated cell cultures, AP and CRP were detected immunohistochemically within hNT neurons, indicating cellular uptake of these proteins. Serum AP at the lowest serum physiological concentration (8 mu g/ml) showed a marked toxicity to hNT neurons. CRP also displayed toxicity to the hNT neurons but at a level compatible with inflammatory states (50 mu g/ml). These results suggest a more direct role for serum AP and CRP in the pathogenesis of AD. (C) 1998 Elsevier Science B.V. All rights reserved.