Inflammatory S100A9 and S100A12 proteins in Alzheimer's disease
Inflammatory S100A9 and S100A12 proteins in Alzheimer's disease
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DOI：
10.1016/j.neurobiolaging.2005.09.033
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发表时间：
2006-11-01
影响因子：
4.2
通讯作者：
Halliday, G. M.
中科院分区：
文献类型：
--
作者：
Shepherd, C. E.;Goyette, J.;Halliday, G. M.
炎症、不溶性蛋白沉积和神经元细胞损失是阿尔茨海默病（AD）脑的重要特征。S100 B与AD的神经病理学特征相关，其中它被认为在神经炎病理学中起作用。S100 A8、S100 A9和S100 A12包含一组新的炎症相关蛋白，其由嗜中性粒细胞组成性表达并在许多炎症细胞中可诱导。我们采用免疫组织化学和Western印迹分析研究了S100 B、S100 A8、S100 A9和S100 A12在散发性和家族性（PS-1）AD病例和对照脑样本中的表达。S100 B、S100 A9和S100 A12与AD的神经病理学特征一致相关，而S100 A8与AD的神经病理学特征无关。Western印迹分析证实，与对照相比，PS-1 AD中可溶性S100 A9显著增加。抗还原的S100 A9复合物在脑提取物中也很明显。在所有病例中均观察到与六聚体S100 A12大小一致的反应性组分。这项研究表明促炎S100 A9和S100 A12在AD炎症和蛋白复合物形成引起的发病机制中具有潜在作用。(c)2005年爱思唯尔公司All rights reserved.
Inflammation, insoluble protein deposition and neuronal cell loss are important features of the Alzheimer's disease (AD) brain. S100B is associated with the neuropathological hallmarks of AD where it is thought to play a role in neuritic pathology. S100A8, S100A9 and S100A12 comprise anew group of inflammation-associated proteins that are constitutively expressed by neutrophils and inducible in numerous inflammatory cells. We investigated expression of S100B, S100A8, S100A9 and S100A12 in brain samples from sporadic and familial (PS-1) AD cases and controls using immunohistochemistry and Western blot analysis. S100B, S100A9 and S100A12, but not S100A8, were consistently associated with the neuropathological hallmarks of AD. Western blot analysis confirmed significant increases in soluble S100A9 in PS-1 AD compared to controls. S100A9 complexes that were resistant to reduction were also evident in brain extracts. A reactive component of a size consistent with hexameric S100A12 was seen in all cases. This study indicates a potential role for pro-inflammatory S100A9 and S100A12 in pathogenesis caused by inflammation and protein complex formation in AD. (c) 2005 Elsevier Inc. All rights reserved.