Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
Division of Bio-Medical Science &Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea.
Mol Neurobiol. 2018 Jun;55(6):5232-5242. doi: 10.1007/s12035-017-0753-6. Epub 2017 Sep 6.
MicroRNAs are small non-coding RNAs that function as regulators of gene expression. The altered expression of microRNAs influences the pathogenesis of Alzheimer's disease. Many researchers have focused on studies based on the relatively distinctive etiology of familial Alzheimer's disease due to the absence of risk factors in the pathogenesis of sporadic Alzheimer's disease. Although there is a limitation in Alzheimer's disease studies, both Alzheimer's disease types have a common risk factor-aging. No study to date has examined the aging factor in Alzheimer's disease animal models with microRNAs. To investigate the effect of aging on the changes in microRNA expressions in the Alzheimer's disease animal model, we selected 37 hippocampal microRNAs whose expression in 12- and 18-month aged mice changed significantly using microRNA microarray. On the basis of bioinformatics databases, 30 hippocampal microRNAs and their putative targets of PSEN1/PSEN2 double knockout mice were included in 28 pathways such as the wnt signaling pathway and ubiquitin-mediated proteolysis pathway. Cortical microRNAs and its putative targets involved in pathological aging were included in only four pathways such as the heparin sulfate biosynthesis. The altered expressions of these hippocampal microRNAs were associated to the imbalance between neurotoxic and neuroprotective functions and seemed to affect neurodegeneration in PSEN1/PSEN2 double knockout mice more severely than in wild-type mice. This microRNA profiling suggests that microRNAs play potential roles in the normal aging process, as well as in the Alzheimer's disease process.
微小 RNA 是一种小的非编码 RNA，作为基因表达的调节剂发挥作用。微小 RNA 的表达改变影响阿尔茨海默病的发病机制。许多研究人员专注于基于家族性阿尔茨海默病相对独特病因的研究，因为散发性阿尔茨海默病的发病机制中没有风险因素。尽管阿尔茨海默病研究存在局限性，但这两种类型的阿尔茨海默病都有一个共同的风险因素——衰老。迄今为止，没有研究检查过阿尔茨海默病动物模型中微小 RNA 与衰老因素的关系。为了研究衰老对阿尔茨海默病动物模型中微小 RNA 表达变化的影响，我们选择了 37 个海马微小 RNA，使用微阵列对其在 12 个月和 18 个月大的小鼠中的表达进行了检测。基于生物信息学数据库，30 个海马微小 RNA 及其 PSEN1/PSEN2 双敲除小鼠的潜在靶点被纳入 28 条途径，如 Wnt 信号通路和泛素介导的蛋白水解通路。皮质微小 RNA 及其潜在靶点参与病理性衰老的通路只有 4 条，如硫酸乙酰肝素生物合成。这些海马微小 RNA 的表达改变与神经毒性和神经保护功能之间的失衡有关，似乎比在野生型小鼠中更严重地影响 PSEN1/PSEN2 双敲除小鼠的神经退行性变。这种微小 RNA 分析表明，微小 RNA 在正常衰老过程以及阿尔茨海默病过程中发挥潜在作用。
