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首页> 外文期刊>The FEBS journal >RCAN1-1L is overexpressed in neurons of Alzheimer's disease patients
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RCAN1-1L is overexpressed in neurons of Alzheimer's disease patients

机译：RCAN1-1L在阿尔茨海默氏病患者的神经元中过表达

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摘要

At least two different isoforms of RCAN1 mRNA are expressed in neuronal cells in normal human brain. Although RCAN1 mRNA is elevated in brain regions affected by Alzheimer's disease, it is not known whether the disease affects neuronal RCAN1, or if other cell types (e.g. astrocytes or microglia) are affected. It is also unknown how many protein isoforms are expressed in human brain and whether RCAN1 protein is overexpressed in Alzheimer's disease. We explored the expression of both RCAN1-1 and RCAN1-4 mRNA isoforms in various cell types in normal and Alzheimer's disease postmortem samples, using the combined technique of immunohistochemistry and in situ hybridization. We found that both exon 1 and exon 4 are predominantly expressed in neuronal cells, and no significant expression of either of the exons was observed in astocytes or microglial cells. This was true in both normal and Alzheimer's disease brain sections. We also demonstrate that RCAN1-1 mRNA levels are approximately two-fold higher in neurons from Alzheimer's disease patients versus non-Alzheimer's disease controls. Using western blotting, we now show that there are three RCAN1 protein isoforms expressed in human brain: RCAN1-1L, RCAN1-1S, and RCAN1-4. We have determined that RCAN1-1L is expressed at twice the level of RCAN1-4, and that there is very minor expression of RCAN1-1S. We also found that the RCAN1-1L protein is overexpressed in Alzheimer's disease patients, whereas RCAN1-4 is not. From these results, we conclude that RCAN1-1 may play a role in Alzheimer's disease, whereas RCAN1-4 may serve another purpose.
机译：正常人脑中的神经元细胞中至少表达两种不同的RCAN1 mRNA亚型。尽管在受阿尔茨海默氏病影响的大脑区域中RCAN1 mRNA升高，但尚不清楚该疾病是否影响神经元RCAN1或其他细胞类型（例如星形胶质细胞或小胶质细胞）是否受到影响。还不清楚在人脑中表达多少蛋白同工型以及RCAN1蛋白在阿尔茨海默氏病中是否过表达。我们使用免疫组织化学和原位杂交技术探讨了正常和阿尔茨海默氏病死后样品中各种细胞类型中RCAN1-1和RCAN1-4 mRNA的同工型的表达。我们发现外显子1和外显子4主要在神经元细胞中表达，并且在星形胶质细胞或小胶质细胞中未观察到任何外显子的显着表达。在正常和阿尔茨海默氏病脑切片中都是如此。我们还证明，与非阿尔茨海默氏病对照相比，来自阿尔茨海默氏病患者的神经元中RCAN1-1 mRNA的水平大约高两倍。使用蛋白质印迹，我们现在显示人脑中表达了三种RCAN1蛋白同工型：RCAN1-1L，RCAN1-1S和RCAN1-4。我们已经确定RCAN1-1L的表达水平是RCAN1-4的两倍，并且RCAN1-1S的表达很小。我们还发现，RCAN1-1L蛋白在阿尔茨海默氏病患者中过表达，而RCAN1-4不是。根据这些结果，我们得出结论，RCAN1-1可能在阿尔茨海默氏病中起作用，而RCAN1-4可能具有其他目的。

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