NDRG2:: a novel Alzheimer's disease associated protein

NDRG2:: a novel Alzheimer's disease associated protein
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DOI:
10.1016/j.nbd.2004.01.003
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发表时间:
2004-06-01
影响因子:
6.1
通讯作者:
Jensen, NA
Jensen, NA
中科院分区:
医学1区
文献类型:
--
作者:
Mitchelmore, C;Büchmann-Moller, S;Jensen, NA

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我们对阿尔茨海默病(AD)相关基因的理解是不完整的。利用消减克隆技术,我们发现α/β-水解酶折叠蛋白基因NDRG 2(NDRG家族成员2)在AD脑中在RNA和蛋白质水平均上调。NDRG 2在受累脑中的表达在(1)皮质锥体神经元、(2)老年斑和(3)营养不良神经元的细胞突起中被揭示。在转基因小鼠的海马锥体神经元中编码长和短NDRG 2亚型的两种剪接变体的过表达导致两种亚型定位于树突状突起。总之,我们的研究结果表明NDRG 2上调与人脑中的疾病发病机制相关,并为AD中发生的分子变化提供了新的见解。(C)2004年爱思唯尔公司All rights reserved.
Our understanding of the genes involved in Alzheimer's disease (AD) is incomplete. Using subtractive cloning technology, we discovered that the alpha/beta-hydrolase fold protein gene NDRG2 (NDRG family member 2) is upregulated at both the RNA and protein levels in AD brains. Expression of NDRG2 in affected brains was revealed in (1) cortical pyramidal neurons, (2) senile plaques and (3) cellular processes of dystrophic neurons. Overexpression of two splice variants encoding a long and short NDRG2 isoform in hippocampal pyramidal neurons of transgenic mice resulted in localization of both isoforms to dendritic processes. Taken together, our findings suggest that NDRG2 upregulation is associated with disease pathogenesis in the human brain and provide new insight into the molecular changes that occur in AD. (C) 2004 Elsevier Inc. All rights reserved.