• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochimica et Biophysica Acta. General Subjects >Identification and functional characterization of a putative IDE, C28F5.4 (ceIDE-1), in Caenorhabditis elegans: Implications for Alzheimer's disease
【24h】

Identification and functional characterization of a putative IDE, C28F5.4 (ceIDE-1), in Caenorhabditis elegans: Implications for Alzheimer's disease

机译：秀丽隐杆线虫中假定的IDE C28F5.4（ceIDE-1）的鉴定和功能表征：对阿尔茨海默氏病的影响

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Insulin-degrading enzyme (IDE) is a zinc metalloprotease, known to degrade insulin peptide and amyloid-beta (A beta); the key protein involved in Alzheimer's disease (AD). Considering the important role played by IDE in disease progression of AD and type 2 diabetes mellitus (T2DM), we endeavored to identify the Caenorhabditis elegans (C. elegans) IDE orthologous genes and test them for their role in AD related outcomes. We employed bioinformatics, reverse genetics and molecular biology approaches towards identification and functional characterization of putative IDE candidates in C. elegans. Using in-silico analysis we have identified seven C elegans genes that possess HXXEH motif, an identifying marker of IDE. We further carried out functional analysis of the identified genes in A beta expressing C elegans strain CL4176 [myo-3/A beta 1-42 long 3'-UTR] via studying effect on A beta induced toxicity, cholinergic neuroanatomy, content of acetylcholine/acetylcholine-esterase, extent of reactive oxygen species and expression of FOXO transcription factor DAF-16. Our findings reveal that amongst the identified putative IDE orthologs, a functionally uncharacterized gene C28F5.4 had a profound effect on the tested endpoints. Knocking down C28F5.4 modulated the AD associated conditions by decreasing A beta induced toxicity, severely compromising cholinergic neuroanatomy, reducing expression of acetylcholine-transporter, decreasing acetylcholine content, elevating ROS, with no effect on DAF-16 stress-response protein. These studies provide crucial insight into the structural/functional orthology of IDEs across human and nematode species and further our understanding of the involvement of these proteins and insulin pathway in AD. Further studies could aid in identifying novel drug-targets and in understanding the common modulating factors between AD and T2DM. (C) 2016 Elsevier B.V. All rights reserved.
机译：胰岛素降解酶（IDE）是锌金属蛋白酶，已知可降解胰岛素肽和淀粉样β（A beta）。涉及阿尔茨海默氏病（AD）的关键蛋白。考虑到IDE在AD和2型糖尿病（T2DM）疾病进展中所起的重要作用，我们致力于鉴定秀丽隐杆线虫（C. elegans）IDE直系同源基因，并测试它们在AD相关结局中的作用。我们采用了生物信息学，反向遗传学和分子生物学方法来鉴定秀丽隐杆线虫中潜在的IDE候选物并进行功能表征。使用计算机内分析，我们已经鉴定了七个具有线粒体C线虫基因，它们是IDE的识别标记HXXEH。我们通过研究对Aβ诱导的毒性，胆碱能神经解剖学，乙酰胆碱/的含量的影响，进一步对表达A beta的秀丽线虫菌株CL4176 [myo-3 / A beta 1-42 long 3'-UTR]中鉴定的基因进行了功能分析。乙酰胆碱酯酶，活性氧的程度和FOXO转录因子DAF-16的表达。我们的发现表明，在确定的推定IDE直系同源基因中，功能上未表征的基因C28F5.4对测试的终点产生了深远的影响。降低C28F5.4通过降低Aβ诱导的毒性，严重损害胆碱能神经解剖，降低乙酰胆碱转运蛋白的表达，降低乙酰胆碱含量，升高ROS来调节AD相关条件，而对DAF-16应激反应蛋白没有影响。这些研究为跨人类和线虫物种的IDE的结构/功能组织学提供了至关重要的见解，并进一步使我们了解了这些蛋白质和胰岛素途径在AD中的参与。进一步的研究可能有助于确定新的药物靶标，并有助于了解AD和T2DM之间的常见调节因素。 （C）2016 Elsevier B.V.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号