Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute, Göttingen, Germany.
EMBO J. 2011 Sep 23;30(20):4299-308. doi: 10.1038/emboj.2011.327.
MicroRNAs are key regulators of transcriptome plasticity and have been implicated with the pathogenesis of brain diseases. Here, we employed massive parallel sequencing and provide, at an unprecedented depth, the complete and quantitative miRNAome of the mouse hippocampus, the prime target of neurodegenerative diseases such as Alzheimer's disease (AD). Using integrative genetics, we identify miR-34c as a negative constraint of memory consolidation and show that miR-34c levels are elevated in the hippocampus of AD patients and corresponding mouse models. In line with this, targeting miR-34 seed rescues learning ability in these mouse models. Our data suggest that miR-34c could be a marker for the onset of cognitive disturbances linked to AD and indicate that targeting miR-34c could be a suitable therapy.
microRNAs 是转录组可塑性的关键调节因子，与脑疾病的发病机制有关。在这里，我们采用大规模平行测序技术，以前所未有的深度提供了小鼠海马体的完整定量 miRNA 组，这是阿尔茨海默病（AD）等神经退行性疾病的主要靶点。通过整合遗传学，我们确定 miR-34c 是记忆巩固的负约束因子，并表明 AD 患者和相应的小鼠模型中海马体中的 miR-34c 水平升高。与此一致的是，靶向 miR-34 种子可以挽救这些小鼠模型的学习能力。我们的数据表明，miR-34c 可能是与 AD 相关认知障碍的起始标志物，并表明靶向 miR-34c 可能是一种合适的治疗方法。
