A novel membrane protein, encoded by the gene covering KIAA0233, is transcriptionally induced in senile plaque-associated astrocytes
A novel membrane protein, encoded by the gene covering KIAA0233, is transcriptionally induced in senile plaque-associated astrocytes
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DOI：
10.1016/j.brainres.2006.06.050
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发表时间：
2006-09-07
期刊：
影响因子：
2.9
通讯作者：
Yamada, Tatsuo
中科院分区：
文献类型：
--
作者：
Satoh, Kazuki;Hata, Mitsumi;Yamada, Tatsuo
淀粉样蛋白(Aβ)沉积和老年斑相关星形胶质细胞是阿尔茨海默病(AD)常见的神经病理特征。虽然Aβ促进神经病变进展的分子机制尚未完全确定，但毫无疑问，Aβ与脑内主要细胞类型星形胶质细胞的联系对疾病的恶化有显著影响。为了确定可能与AD进展密切相关的星形细胞来源的分子，我们鉴定了一个新的Aβ诱导的大鼠基因，命名为Mib，其人类同源基因涵盖KIAA0233。MIB基因转染的C6细胞在内质网和内质网高尔基体中间区表达Mib蛋白。为了评估Mib在AD中的作用，我们研究了它在AD脑中的表达。在非阿尔茨海默病患者的大脑中，Mib mRNA在神经元中被检测到，但在静止的星形胶质细胞中没有被检测到。相反，在AD脑中，Mib mRNA在与老年斑相关的激活星形胶质细胞中表达，但在病变周围的神经元中不表达。根据这些观察，Mib似乎是一个新的Aβ反应基因，可能在AD大脑中老年斑周围的星形胶质细胞炎症激活中发挥作用。(C)2006爱思唯尔B.V.保留所有权利。
Beta-amyloid (A beta) deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease (AD). Although the molecular mechanisms by which A beta contributes to the progression of neuropathologic changes have not been entirely established, there is little doubt that the association of A beta with astrocytes, the predominant cell type in brain, significantly influences exacerbation of the disease. In an effort to identify astrocyte-derived molecules that may be intimately associated with progression of AD, we identified a novel A beta-induced rat gene, designated Mib, whose human counterpart covers KIAA0233. Mib-transfected C6 cells express Mib protein in the endoplasmic reticulum and endplasmic reticulum-Golgi-intermediate compartment. To evaluate roles of Mib in AD, we investigated its expression in the AD brain. In non-AD brains, Mib mRNA has been detected in neurons but not in quiescent astrocytes. On the contrary, in AD brains, Mib mRNA is expressed in activated astrocytes associated with senile plaques, but not expressed in neurons around lesions. From these observations, Mib appears to be a novel A beta-responsive gene that may play a role in astrocyte inflammatory activation around senile plaques in the AD brain. (c) 2006 Elsevier B.V. All rights reserved.