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Advances in the role of microRNAs in lipid metabolism-related anti-atherosclerotic drug discovery

机译:microRNA在脂质代谢相关抗动脉粥样硬化药物发现中的作用研究进展

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Introduction: Atherosclerosis is one of the leading causes of mortality in industrialized and developing nations and there remains a large unmet medical need for new therapeutic approaches. Therefore, efforts are continuing needed to discover and develop novel drugs based on the advances in the understanding of molecular basis in lipid metabolism, especially a critical role of miRNAs in regulating lipid metabolism. miRNAs are endogeneous non-coding small RNAs that regulate gene expression on the post-transcriptional level. Some miRNAs have been proposed as potential targets in anti-atherosclerotic drug discovery. Areas covered: This review provides a summary of recently reported miRNAs which are functioning in various pathways of lipid metabolism. Furthermore, this review describes the strategies currently employed for the miRNA-based drug discovery, including: the development of antisense oligonucleotides targeting the specific miRNAs directly and the discovery of small molecules targeting the miRNA activity or biogenesis by application of biochemical or cell-based screening assays. Expert opinion: miRNAs play a prominent role in lipid metabolism and provide intriguing therapeutic targets, which add a new dimension for anti-atherosclerotic drug discovery. Translation of these targets and strategies for drug discovery, although still challenging, has shown a promising potential for a more effective reduction in atherosclerotic risk in the future.
机译:简介:动脉粥样硬化是工业化国家和发展中国家导致死亡的主要原因之一,医疗对新治疗方法的需求仍未得到满足。因此,基于对脂质代谢的分子基础的理解的进展,尤其是miRNA在调节脂质代谢中的关键作用,基于发现的进展,需要继续努力以发现和开发新药。 miRNA是内源性非编码小RNA,可在转录后水平上调节基因表达。已经提出了一些miRNAs作为抗动脉粥样硬化药物发现中的潜在靶标。涵盖领域:这篇综述总结了最近报道的miRNA,它们在脂质代谢的各种途径中起作用。此外,本综述描述了目前用于基于miRNA的药物发现的策略,包括:直接针对特定miRNA的反义寡核苷酸的开发以及通过应用生化或基于细胞的筛选发现针对miRNA活性或生物发生的小分子的发现分析。专家意见:miRNA在脂质代谢中起着重要作用,并提供有趣的治疗靶点,为抗动脉粥样硬化药物的发现增加了新的领域。这些目标和药物发现策略的翻译尽管仍然具有挑战性,但已显示出在将来更有效降低动脉粥样硬化风险的潜力。

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