A novel alternative splice variant of nicastrin and its implication in Alzheimer disease
A novel alternative splice variant of nicastrin and its implication in Alzheimer disease
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DOI：
10.1016/j.lfs.2005.10.007
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发表时间：
2006-04-18
期刊：
影响因子：
6.1
通讯作者：
Miki, T
中科院分区：
文献类型：
--
作者：
Mitsuda, N;Yamagata, HD;Miki, T
尼卡斯特林主要通过跨膜结构域n端三分之一与γ -分泌酶复合物组分相互作用。真正的跨膜结构域对于与γ -分泌酶复合物组分的相互作用和活性γ -分泌酶复合物的形成至关重要。在这项研究中，我们在人脑组织中鉴定了一种新的nicastron的选择性剪接转录物。该转录物（NCSTN-Delta E16）缺乏nicastrin mRNA的第16外显子，导致其跨膜结构域上游的71个氨基酸缺失。分析其在病理诊断为阿尔茨海默病（病例）和非阿尔茨海默病（对照组）患者海马中的表达模式。在携带APOE-epsilon 4等位基因的患者中，NCSTN-Delta e16阳性组阿尔茨海默病的发病率似乎有所增加，但相关性无统计学意义。综上所述，除了ApoE-epsilon 4等位基因的风险外，NCSTN-Delta E16转录本的表达可能会增加患阿尔茨海默病的风险。有必要在更大规模的人群中进行进一步的研究，以确定其在阿尔茨海默病中的潜在意义。(c) 2005 Elsevier Inc .版权所有
Nicastrin interacts with gamma-secretase complex components predominantly via the N-terminal third of the transmembrane domain. The authentic transmembrane domain is critically required for the interaction with gamma-secretase complex components and for formation of an active gamma-secretase complex. In this study, we have identified a novel alternatively spliced transcript of nicastrun in human brain tissue. This transcript (NCSTN-Delta E16) lacks exon 16 of nicastrin mRNA, which leads to deletion of 71 amino acids just upstream of its transmembrane domain. Its expression pattern was analyzed in the hippocampus of patients with pathologically diagnosed Alzheimer disease (cases) and non-Alzheimer dementia (controls). In patients with the APOE-epsilon 4 allele, the frequency of Alzheimer disease appeared to be increased in the NCSTN-Delta E16-positive group, but the association was not statistically significant. In conclusion, the expression of NCSTN-Delta E16 transcript may confer some additional risk for developing Alzheimer disease beyond the risk due to ApoE-epsilon 4 allele. Further investigation in larger scale population would be necessary to address its potential implication in Alzheimer disease. (c) 2005 Elsevier Inc All rights reserved.