MicroRNAs in neurodegenerative diseases and their therapeutic potential.
MicroRNAs in neurodegenerative diseases and their therapeutic potential.
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DOI：
10.1016/j.pharmthera.2011.10.002
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发表时间：
2012-02
影响因子：
13.5
通讯作者：
Mouradian, M. Maral
中科院分区：
文献类型：
--
作者：
Junn, Eunsung;Mouradian, M. Maral
MicroRNA (miRNA) 是丰富的、内源性的、短的非编码 RNA，通过与目标 mRNA 碱基配对，充当基因表达的重要转录后调节因子。在过去的十年中，人们积累了大量关于 miRNA 的生物发生、其分子机制以及在各种细胞环境中的功能作用的知识。阿尔茨海默病和帕金森病等神经退行性疾病患者大脑中某些 miRNA 分子表达的改变表明 miRNA 在这些疾病中可能发挥着至关重要的调节作用。 miRNA 靶位点的多态性也可能构成疾病风险的重要决定因素。此外，新出现的证据表明特定 miRNA 靶向并调节对疾病发病机制至关重要的特定蛋白质的表达。考虑到易感神经元群体中这些蛋白质的数量似乎对神经退行性变至关重要，miRNA 介导的调节代表了具有重要治疗前景的新靶点。在这篇综述中，讨论了 miRNA 在几种神经退行性疾病中的影响及其作为治疗干预措施的潜力。
MicroRNAs (miRNAs) are abundant, endogenous, short, noncoding RNAs that act as important post-transcriptional regulators of gene expression by base-pairing with their target mRNA. During the last decade, substantial knowledge has accumulated regarding the biogenesis of miRNAs, their molecular mechanisms and functional roles in a variety of cellular contexts. Altered expression of certain miRNA molecules in the brains of patients with neurodegenerative diseases such as Alzheimer and Parkinson suggests that miRNAs could have a crucial regulatory role in these disorders. Polymorphisms in miRNA target sites may also constitute an important determinant of disease risk. Additionally, emerging evidence points to specific miRNAs targeting and regulating the expression of particular proteins that are key to disease pathogenesis. Considering that the amount of these proteins in susceptible neuronal populations appears to be critical to neurodegeneration, miRNA-mediated regulation represents a new target of significant therapeutic prospects. In this review, the implications of miRNAs in several neurodegenerative disorders and their potential as therapeutic interventions are discussed.
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