Expression of suppressor of cytokine signaling genes in human elderly and Alzheimer's disease brains and human microglia.
Expression of suppressor of cytokine signaling genes in human elderly and Alzheimer's disease brains and human microglia.
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DOI：
10.1016/j.neuroscience.2014.09.052
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发表时间：
2015-08-27
期刊：
影响因子：
3.3
通讯作者：
Lue, L. -F.
中科院分区：
文献类型：
--
作者：
Walker, D. G.;Whetzel, A. M.;Lue, L. -F.
存在多种细胞系统来防止脑组织失控的炎症；细胞因子信号(SOCS)蛋白的抑制物在这些过程中起着关键作用。SOCS蛋白通过促进激活受体的降解和去除持续激活的刺激而参与限制细胞信号通路。有八个不同的SoCs基因编码具有相似结构和特性的蛋白质。所有的SoCS蛋白都可以减少激活的转录因子JAK和STAT的信号转导，但它们也调节许多其他的信号通路。SOCS-1和SOCS-3在调节炎症过程中具有特殊的作用。慢性炎症是阿尔茨海默病(AD)影响大脑的一个主要病理特征，其原因是对淀粉样斑块或神经原纤维缠结的反应，这是AD的病理特征。本研究的目的是检测SOCS基因在人类非痴呆(ND)和AD脑以及人脑来源的小胶质细胞中的表达，以确定AD相关的病理是否导致这些关键分子的缺失。我们发现，在Aβ和炎症刺激的小胶质细胞中，SOCS-1、SOCS-2、SOCS-3和CIS的mRNA表达增加，而SOCS-6mRNA的表达在两种处理方式下都降低。从ND和AD患者的颞叶皮质标本中可以检测到SoCS-1到SOCS-7和CIS的mRNA和SoCS-1到SOCS-7的蛋白。阿尔茨海默病大鼠脑内SOCS-2、SOCS-3和CIS基因的表达水平显著升高，SOCS-4和SOCS-7的蛋白表达水平显著升高。总而言之，没有证据表明这些关键的炎症调节蛋白在老年人或阿尔茨海默病患者的大脑中存在缺陷。
Multiple cellular systems exist to prevent uncontrolled inflammation in brain tissues; the Suppressor of cytokine signaling (SOCS) proteins have key roles in these processes. SOCS proteins are involved in restricting cellular signaling pathways by enhancing the degradation of activated receptors and removing the stimuli for continued activation. There are eight separate SOCS genes that code for proteins with similar structures and properties. All SOCS proteins can reduce signaling of activated transcription factors JAK and STAT, but they also regulate many other signaling pathways. SOCS-1 and SOCS-3 have particular roles in regulating inflammatory processes. Chronic inflammation is a key feature of the pathology present in Alzheimer’s disease (AD)-affected brains resulting from responses to amyloid plaques or neurofibrillary tangles, the pathological hallmarks of AD. The goal of this study was to examine SOCS gene expression in human non-demented (ND) and AD brains and in human brain-derived microglia to determine if AD-related pathology resulted in a deficit of these critical molecules. We demonstrated that SOCS-1, SOCS-2, SOCS-3 and CIS mRNA expression was increased in Aβ– and inflammatory-stimulated microglia, while SOCS-6 mRNA expression was decreased by both types of treatments. Using human brain samples from temporal cortex from ND and AD cases, SOCS-1 through SOCS-7 and CIS mRNA and SOCS-1 through SOCS-7 protein could be detected constitutively in ND and AD human brain samples. Although, the expression of key SOCS genes did not change to a large extent as a result of AD pathology, there were significantly increased levels of SOCS-2, SOCS-3 and CIS mRNA and increased protein levels of SOCS-4 and SOCS-7 in AD brains. In summary, there was no evidence of a deficit of these key inflammatory regulating proteins in aged or AD brains.
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影响因子：
9.3
作者：
Cribbs DH;Berchtold NC;Perreau V;Coleman PD;Rogers J;Tenner AJ;Cotman CW
通讯作者：
Cotman CW
影响因子：
3.7
作者：
Collins AS;McCoy CE;Lloyd AT;O'Farrelly C;Stevenson NJ
通讯作者：
Stevenson NJ
影响因子：
4.4
作者：
Ehlting, Christian;Lai, Wi S.;Bode, Johannes G.
通讯作者：
Bode, Johannes G.
影响因子：
9.3
作者：
Colton CA;Mott RT;Sharpe H;Xu Q;Van Nostrand WE;Vitek MP
通讯作者：
Vitek MP
影响因子：
3
作者：
Gonzalez Y;Herrera MT;Soldevila G;Garcia-Garcia L;Fabián G;Pérez-Armendariz EM;Bobadilla K;Guzmán-Beltrán S;Sada E;Torres M
通讯作者：
Torres M