Huntington’s disease (HD) is an intractable neurodegenerative disorder caused by mutant Huntingtin (HTT) proteins that adversely affect various biomolecules and genes. MicroRNAs (miRNAs), which are functional small non-coding RNAs, are also affected by mutant HTT proteins. Here, we show amelioration in motor function and lifespan of HD-model mice, R6/2 mice, by supplying miR-132 to HD brains using a recombinant adeno-associated virus (rAAV) miRNA expression system. miR-132 is an miRNA related to neuronal maturation and function, but the level of miR-132 in the brain of R6/2 mice was significantly lower than that of wild-type mice. Our miR-132 supplemental treatment, i.e., supplying miR-132 to the brain, produced symptomatic improvement or retarded disease progression in R6/2 mice; interestingly, it had little effect on disease-causing mutant HTT mRNA expression and its products. Therefore, the findings suggest that there may be a therapeutic way to treat HD without inhibiting and/or repairing disease-causing HTT genes and gene products. Although miR-132 supplement may not be a definitive treatment for HD, it may become a therapeutic method for relieving HD symptoms and delaying HD progression.

亨廷顿舞蹈病（HD）是一种难治性神经退行性疾病，由突变的亨廷顿蛋白（HTT）引起，对各种生物分子和基因产生不利影响。微小RNA（miRNA）是功能性小型非编码RNA，也受到突变型HTT蛋白的影响。在这里，我们通过使用重组腺相关病毒（rAAV）miRNA表达系统向mi脑提供miR-132，显示了HD模型小鼠R6 / 2小鼠的运动功能和寿命的改善。miR-132是与神经元成熟和功能有关的miRNA，但R6 / 2小鼠的大脑中miR-132的水平明显低于野生型小鼠。我们的miR-132补充治疗，即提供miR-132R6 / 2小鼠的大脑症状改善或疾病进展受阻；有趣的是，它对引起疾病的突变体HTT mRNA表达及其产物几乎没有影响。因此，这些发现表明，可能存在一种治疗HD而不抑制和/或修复引起疾病的HTT基因和基因产物的治疗方法。尽管miR-132补充剂可能不是HD的确切治疗方法，但它可能成为缓解HD症状和延迟HD进展的治疗方法。