MicroRNAs as effectors of brain function.
MicroRNAs as effectors of brain function.
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DOI：
10.1161/strokeaha.113.000985
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发表时间：
2013-06
期刊：
影响因子：
8.3
通讯作者：
Saugstad JA
中科院分区：
文献类型：
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作者：
Saugstad JA
在发现后相对较短的时间内，miRNAs已被证明对神经元发育、存活、功能和可塑性至关重要。miRNAs在缺血和缺血预处理中受到调节，雄性和雌性小鼠对缺血表现出共同和独特的反应，这可能有助于对缺血的性二态反应。这些发现保证了进一步的研究，以检查缺血调节的miRNA对细胞死亡和/或神经保护的作用，并确定新的靶点，用于治疗或预防中风的替代策略。鉴于miRNA在基因组内编码，可以想象，miRNA基因和/或其mRNA靶序列中的突变可能破坏正常的转录后基因调控并导致疾病表型。对于家族性疾病，如中风，这可能是特别真实的，其中蛋白质编码基因突变尚未被确定。miRNA也迅速成为疾病的生物标志物，包括脑损伤，神经退行性疾病和精神疾病。22因此，有证据表明从缺血性中风患者分离的外周血中的miRNA表达改变，23，24表明血液miRNA可用作脑损伤（包括脑缺血）的生物标志物的可能性。miRNA研究的第一个十年极大地影响了我们对正常和改变细胞功能的机制的理解，尽管由于miRNA的复杂性而存在技术限制。在未来十年的miRNA研究中，应该全力支持推进和发展分析和验证miRNA所需的工具，因为这些工具对于建立miRNA介导的转录后基因表达与疾病之间的直接相关性至关重要，这对人类健康至关重要。
In the relatively short time since their discovery, the miRNAs have been shown to be essential for neuronal development, survival, function, and plasticity. MiRNAs are regulated in response to ischemia and ischemic preconditioning, and male and female mice show both common and unique responses to ischemia, which may contribute to sexually dimorphic responses to ischemia. These findings warrant further studies to examine the role of ischemia-regulated miRNAs on cell death and/or neuroprotection and to identify new targets for alternative strategies for the treatment or prevention of stroke. Given that miRNAs are encoded within the genome, it is conceivable that mutations in miRNA genes and/or their mRNA target sequences, could disrupt normal post-transcriptional gene regulation and lead to disease phenotypes. This may be particularly true for familial diseases, such as stroke, where protein coding gene mutations have not been identified. MiRNAs are also rapidly emerging as biomarkers for diseases, including brain injury, neurodegeneration, and psychiatric disorders. 22 Accordingly, there is evidence for altered miRNA expression in peripheral blood isolated from ischemic stroke patients, 23, 24 suggesting the possibility that blood miRNAs can be used as biomarkers for brain injury, including cerebral ischemia. The first decade of miRNA research has greatly impacted our understanding of the mechanisms underlying normal and altered cellular function, despite technical limitations due to the complexity of miRNAs. In the next decade of miRNA studies, efforts to advance and evolve the tools necessary for analysis and validation of miRNAs, should be fully supported, as these tools will be essential in establishing direct correlations between miRNA-mediated posttranscriptional gene expression and disease, a matter of great importance to human health.