Role of miR-211 in Neuronal Differentiation and Viability: Implications to Pathogenesis of Alzheimer's Disease.
Role of miR-211 in Neuronal Differentiation and Viability: Implications to Pathogenesis of Alzheimer's Disease.
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miR-211 在神经元分化和活力中的作用：对阿尔茨海默病发病机制的影响
DOI：
10.3389/fnagi.2016.00166
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发表时间：
2016
影响因子：
4.8
通讯作者：
Wan J
中科院分区：
文献类型：
--
作者：
Fan C;Wu Q;Ye X;Luo H;Yan D;Xiong Y;Zhu H;Diao Y;Zhang W;Wan J
阿尔茨海默病（Alzheimer's disease，AD）是一种以细胞外β淀粉样蛋白（β Amyloid，Aβ）沉积、细胞内神经元缠结和神经元丢失为特征的不可逆性神经退行性疾病。神经发生功能障碍和神经元变性加重是AD的发病机制之一。我们现在报道，miR-211- 5 p，一种小的非编码RNA，可以通过直接靶向NUAK 1来损害神经突分化，降低神经元活力并加速Aβ诱导的病理学进展。在本研究中，我们观察到在胚胎发育过程中，miR-211- 5 p在小鼠正常大脑皮层中的表达水平下调。然而，在APPswe/PS1ΔE9双转基因成年小鼠中，与年龄匹配的野生型小鼠相比，从9月龄开始上调。在原代皮层神经元培养物中的研究表明，miR-211- 5 p可以通过NUAK 1抑制来抑制神经突生长和分支，并降低成熟神经元活力。在Aβ作用下，损伤更为明显。我们的数据显示miR-211- 5 p可以抑制皮层神经元的分化和存活，这可能是AD中突触失效、神经元丢失和认知功能障碍的原因之一。
Alzheimer’s disease (AD) is an age-related irreversible neurodegenerative disorder characterized by extracellular β Amyloid(Aβ) deposition, intracellular neurofibrillary tangles and neuronal loss. The dysfunction of neurogenesis and increased degeneration of neurons contribute to the pathogenesis of AD. We now report that miR-211-5p, a small non-coding RNA, can impair neurite differentiation by directly targeting NUAK1, decrease neuronal viability and accelerate the progression of Aβ-induced pathologies. In this study, we observed that during embryonic development, the expression levels of miR-211-5p were down-regulated in the normal cerebral cortexes of mice. However, in APPswe/PS1ΔE9 double transgenic adult mice, it was up-regulated from 9 months of age compared to that of the age-matched wild type mice. Studies in primary cortical neuron cultures demonstrated that miR-211-5p can inhibit neurite growth and branching via NUAK1 repression and decrease mature neuron viability. The impairments were more obvious under the action of Aβ. Our data showed that miR-211-5p could inhibit cortical neuron differentiation and survival, which may contribute to the synaptic failure, neuronal loss and cognitive dysfunction in AD.