摘要
在老年人群中,阿尔茨海默病(AD)是痴呆的常见原因。它的病理特征包括:老年斑、神经纤维缠结和神经元死亡。科学家们建立了多种AD动物模型,包括酵母、秀丽隐杆线虫、果蝇、小鼠、大鼠和非人灵长类动物。果蝇动物模型在基因操作和筛选实验方面比哺乳动物有更好的有效率。microRNAs (miRNAs) 是长约22nt,调整转录后基因表达水平的小RNA分子。miRNAs调控异常通过影响靶向分子表达和功能参与AD进展。然而,还没有研究出AD果蝇的miRNA 表达谱。采用最新的µParaflo™ miRNA微点阵分析方法,在成年型果蝇AD大脑中均表现异常:其中8种上调(miR- 8, miR-13b, miR-277, miR-279, miR-981, miR-995, miR-998, miR-1017) ,9种下调 (let-7, miR-1, miR-9a, miR-184, miR-193, miR-263b, miR-276a, miR-285, miR-289)。采用Targetscan 软件预测DIANA miRPath 或靶向分子的方法,KEGG pathway注释系统识别了7种通路(赖氨酸、亮氨酸和异亮氨酸退化;MAPK信号通路;背腹轴形成;丙酸通路;鞘脂类代谢;赖氨酸退化;Jak- STAT信号转导通路),7种通路也许受这些miRNAs的影响。miRNA/mRNA 调控网络整合分析揭示在AD中拥有赖氨酸活性的功能束由miRNAs 潜在地调控。总之,我们的表达谱实验可以识别成人型AD果蝇miRNAs 基因标记物。miRNA谱调控异常可能通过扰乱大脑中氨基酸代谢参与AD发病机制。
关键词: 成人型,阿尔茨海默病,氨基酸,果蝇,microRNA,微阵列,谱
Current Alzheimer Research
Title:MicroRNA Expression Analysis of Adult-Onset Drosophila Alzheimer`s Disease Model
Volume: 11 Issue: 9
Author(s): Yan Kong, Jianban Wu and Liudi Yuan
Affiliation:
关键词: 成人型,阿尔茨海默病,氨基酸,果蝇,microRNA,微阵列,谱
摘要: Alzheimer’s disease (AD) is the most common reason for dementia in elderly population. Its neuropathological features include senile plaques, neurofibril tangles and neuronal death. Scientists have established many AD animal models, including yeast, Caenorhabditis elegans, Drosophila melanogaster, mice, rats and non-human primates. Drosophila AD models are much more efficient for genetic manipulation and screening assay than mammals. microRNAs (miRNAs) are ~22nt small RNA molecules that fine-tune gene expression at posttranscriptional level. The dysregulation of miRNAs could participate in AD progression by influencing targets’ expression and functions. However, miRNA expression profile of AD flies has not yet been investigated. Using the latest µParaflo™ miRNA microarray assay, we found that 17 miRNAs that were consistently dysregulated in adult-onset AD Drosophila brains: eight of which were upregulated (miR- 8, miR-13b, miR-277, miR-279, miR-981, miR-995, miR-998, miR-1017) and nine were downregulated (let-7, miR-1, miR-9a, miR-184, miR-193, miR-263b, miR-276a, miR-285, miR-289). KEGG pathway annotations using DIANA miRPath or targets predicted by Targetscan identified 7 pathways (Valine, leucine and isoleucine degradation; MAPK signaling pathway; Dorso-ventral axis formation; Propanoate metabolism; Sphingolipid metabolism; Lysine degradation; Jak- STAT signaling pathway) which might be influenced by these miRNAs. Integrative miRNA/mRNA regulatory network analysis revealed functional cluster with transaminase activity to be potentially regulated by miRNAs in AD. Taken together, our profiling assay identified miRNAs as markers for adult onset AD Drosophila. Dysregulation of miRNA profile may participate in AD pathogenesis by interrupting the metabolism of amino acids in the brain.
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Cite this article as:
Kong Yan, Wu Jianban and Yuan Liudi, MicroRNA Expression Analysis of Adult-Onset Drosophila Alzheimer`s Disease Model, Current Alzheimer Research 2014; 11 (9) . https://dx.doi.org/10.2174/1567205011666141001121416
DOI https://dx.doi.org/10.2174/1567205011666141001121416 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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