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微小RNA与阿尔茨海默病小鼠模型:当前见解与未来研究方向

MicroRNAs and Alzheimer's Disease Mouse Models: Current Insights and Future Research Avenues.

作者信息

Delay Charlotte, Hébert Sébastien S

机构信息

Axe Neurosciences, Centre de Recherche du CHUQ (CHUL), Québec, QC, Canada G1V4G2.

出版信息

Int J Alzheimers Dis. 2011;2011:894938. doi: 10.4061/2011/894938. Epub 2011 Jul 31.

Abstract

Evidence from clinical trials as well as from studies performed in animal models suggest that both amyloid and tau pathologies function in concert with other factors to cause the severe neurodegeneration and dementia in Alzheimer's disease (AD) patients. Accumulating data in the literature suggest that microRNAs (miRNAs) could be such factors. These conserved, small nonprotein-coding RNAs are essential for neuronal function and survival and have been implicated in the regulation of key genes involved in genetic and sporadic AD. The study of miRNA changes in AD mouse models provides an appealing approach to address the cause-consequence relationship between miRNA dysfunction and AD pathology in humans. Mouse models also provide attractive tools to validate miRNA targets in vivo and provide unique platforms to study the role of specific miRNA-dependent gene pathways in disease. Finally, mouse models may be exploited for miRNA diagnostics in the fight against AD.

摘要

来自临床试验以及在动物模型中进行的研究的证据表明,淀粉样蛋白和tau病理与其他因素协同作用,导致阿尔茨海默病(AD)患者出现严重的神经退行性变和痴呆。文献中不断积累的数据表明,微小RNA(miRNA)可能就是这样的因素。这些保守的小型非蛋白质编码RNA对神经元功能和存活至关重要,并与遗传性和散发性AD中涉及的关键基因的调控有关。对AD小鼠模型中miRNA变化的研究为解决miRNA功能障碍与人类AD病理之间的因果关系提供了一种有吸引力的方法。小鼠模型还提供了有吸引力的工具来在体内验证miRNA靶点,并提供独特的平台来研究特定miRNA依赖性基因途径在疾病中的作用。最后,小鼠模型可用于AD防治中的miRNA诊断。

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