Expression of CD74 is increased in neurofibrillary tangles in Alzheimer's disease.
Expression of CD74 is increased in neurofibrillary tangles in Alzheimer's disease.
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DOI：
10.1186/1750-1326-3-13
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发表时间：
2008-09-11
影响因子：
15.1
通讯作者：
Casadesus G
中科院分区：
文献类型：
--
作者：
Bryan KJ;Zhu X;Harris PL;Perry G;Castellani RJ;Smith MA;Casadesus G
阿尔茨海默病（Alzheimer disease，AD）是一种以进行性记忆丧失为特征的慢性神经退行性疾病。AD的病理学标志物包括神经元缠结、淀粉样蛋白-β斑块的积累、神经元损失和炎症。导致神经元功能障碍和丧失的确切事件尚未完全了解。然而，促炎细胞因子，如白细胞介素-1 β、白细胞介素-6和肿瘤坏死因子α，在AD中增加，沿着主要组织相容性复合体（MHC）II类分子和巨噬细胞移动抑制因子（MIF）的基因表达。MHC II类分子存在于大脑的小胶质细胞中，而MIF存在于下丘脑、海马和皮质的小胶质细胞和神经元中。MIF不仅是一种淋巴细胞介质，也是一种具有内分泌特性的垂体因子，可介导细胞外信号调节激酶-1/2 MAP激酶途径的磷酸化。在这项研究中，我们研究了CD 74，这是一种完整的膜蛋白，既可以作为MHC II类分子的伴侣，也可以作为MIF的受体结合位点。最近发现，与年龄匹配的对照组相比，AD病例中的小胶质细胞中CD 74增加，但在神经元中尚未报道。在我们的分析中，免疫组织化学显示CD 74主要在神经元缠结、淀粉样蛋白-β斑块和小胶质细胞中显著增加。这是我们所知的第一个发现，与年龄匹配的对照病例相比，AD病例的神经元中CD 74增加。
Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by progressive memory loss. Pathological markers of AD include neurofibrillary tangles, accumulation of amyloid-β plaques, neuronal loss, and inflammation. The exact events that lead to the neuronal dysfunction and loss are not completely understood. However, pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor α, are increased in AD, along with gene expression of major histocompatibility complex (MHC) class II molecules and macrophage migration inhibitory factor (MIF). MHC class II molecules are found in microglia of the brain, while MIF is found in both microglia and neurons of the hypothalamus, hippocampus, and cortex. MIF is not only a lymphocyte mediator but also a pituitary factor with endocrine properties and can mediate phosphorylation of the extracellular signal-regulated kinase-1/2 MAP kinases pathway. In this study, we looked at CD74, an integral membrane protein that acts as both a chaperone for MHC class II molecules as well as a receptor binding site for MIF. CD74 was recently found to be increased in microglia in AD cases compared to age-matched controls, but has not been reported in neurons. In our analysis, immunohistochemistry revealed a significant increase in CD74 primarily in neurofibrillary tangles, amyloid-β plaques, and microglia. This is the first finding to our knowledge that CD74 is increased in neurons of AD cases compared to age-matched control cases.
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影响因子：
1.7
作者：
Perry, G;Roder, H;Smith, MA
通讯作者：
Smith, MA
影响因子：
20.3
作者：
Starlets, Diana;Gore, Yael;Shachar, Idit
通讯作者：
Shachar, Idit
影响因子：
4.8
作者：
Hoshino, Tatsuya;Nakaya, Tadashi;Mizushima, Tohru
通讯作者：
Mizushima, Tohru
DOI：
10.1196/annals.1347.020
发表时间：
2005-01-01
期刊：
FUTURE OF HORMONE THERAPY: WHAT BASIC SCIENCE AND CLINICAL STUDIES TEACH US
影响因子：
--
作者：
Webber, KM;Casadesus, G;Smith, MA
通讯作者：
Smith, MA
影响因子：
4.7
作者：
Zhu, XW;Sun, Z;Smith, MA
通讯作者：
Smith, MA